A Phase I, 2-part (Part 1 Being a Single Dose Escalation and Part 2, a Parallel Group) Study of Toll-like Receptor (TLR4) Agonist (GSK1795091) in Healthy Subjects

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02798978
• Collaborator: (none)
• Enrollment: 42
• Location: 1
• Arms: 3
• Actual Duration (Months): 9.1
• Patients Per Site Per Month: 4.6

Study Details

Study Description

Brief Summary

This study is an ascending dose first-time-in-human study to determine the safety, tolerability, pharmacodynamic (PD), and pharmacokinetics (PK) profile of GSK1795091 in healthy subjects. The results will support the design of future clinical trials of GSK1795091 administered to subjects with advanced malignancies in combination with immune system modulators.

Part 1 will be a randomized, double-blind (sponsor-unblinded), placebo-controlled, single center, single dose escalation, sequential group evaluation of intravenously administered GSK1795091 to evaluate the safety and tolerability in healthy subjects. Part 2 will be an open-label, parallel group evaluation of 2 doses of GSK1795091 administered, either 1 week apart (Part 2, Cohort 1) or 2 weeks apart (Part 2, Cohort 2). In Part 2, on Day 1, subjects will receive intravenous GSK1795091 at a dose determined by results from Part 1. The total duration of this study is approximately 10 weeks from screening to the last study visit.

Condition or Disease	Intervention/Treatment	Phase
Cancer; Neoplasms	Drug: GSK1795091; Drug: Placebo	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 42 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A 2-part Randomized, Double-blind (Sponsor-unblinded), Placebo-controlled, Ascending Dose and Parallel Group Study of TLR4 Agonist (GSK1795091) Administered to Healthy Subjects
• Actual Study Start Date: Jan 10, 2017
• Actual Primary Completion Date: Oct 13, 2017
• Actual Study Completion Date: Oct 13, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Part 1: GSK1795091 or Placebo In Part 1, subjects in sequential cohorts will receive single ascending doses of intravenous (IV) injection of GSK1795091 or matching placebo, with a starting dose of 7 nanogram (ng), on Day 1 until the highest dose is evaluated.	Drug: GSK1795091; GSK1795091 will be supplied as solution for injection vial. Each 5 mL vial contains 0.001 milligram/mL (mg/mL; 1000 ng/mL) or 0.0001 mg/mL (100 ng/mL)of GSK1795091 and will be administered as IV bolus over 2-5 minutes (min) followed by a IV bolus of 10 mL normal saline.; Drug: Placebo; Matching placebo will be supplied as a solution for injection vial and will be administered as IV bolus over 2-5 min followed by a IV bolus of 10 mL normal saline
Experimental: Part 2 Cohort 1: GSK1795091 In Part 2 Cohort 1, subjects will receive IV injection of GSK1795091 on Day 1, at dose determined in part 1, and second dose on Day 8 (one week apart)	Drug: GSK1795091; GSK1795091 will be supplied as solution for injection vial. Each 5 mL vial contains 0.001 milligram/mL (mg/mL; 1000 ng/mL) or 0.0001 mg/mL (100 ng/mL)of GSK1795091 and will be administered as IV bolus over 2-5 minutes (min) followed by a IV bolus of 10 mL normal saline.
Experimental: Part 2 Cohort 2: GSK1795091 In Part 2 Cohort 2, subjects will receive IV injection of GSK1795091 on Day 1, at dose determined in part 1, and a second dose on Day 15 (two weeks apart)	Drug: GSK1795091; GSK1795091 will be supplied as solution for injection vial. Each 5 mL vial contains 0.001 milligram/mL (mg/mL; 1000 ng/mL) or 0.0001 mg/mL (100 ng/mL)of GSK1795091 and will be administered as IV bolus over 2-5 minutes (min) followed by a IV bolus of 10 mL normal saline.

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Non-serious Adverse Events (AE) and Serious Adverse Events (SAE) [Up to Day 32]

   An AE is any untoward medical occurrence in a clinical investigation 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, any other situation according to medical or scientific judgment or events associated with liver injury and impaired liver function were categorized as SAE. All participants enrolled into the study who have received a dose of study medication (GSK1795091 or placebo) were included in the All Subjects Population. Participants with non-serious AEs (5 percentage threshold) and SAEs has been reported.

2. Change From Baseline in Body Temperature Part 1 [Baseline, Day 1 (1, 2, 4, 6, 8, 12, 16 hours), Day 2, Day 3, Day 4, Day 5, and Day 7.]

   Body temperature was measured in semi-supine position after 5 minutes rest. Baseline values are the last non-missing pre-dose assessments. Change from Baseline was defined as difference between the post-Baseline visit value and the Baseline value.

3. Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) Part 1 [Baseline, Day 1 (1, 2, 4, 6, 8, 12, 16 hours), Day 2, Day 3, Day 4, Day 5, and Day 7.]

   Systolic and diastolic BP was measured in semi-supine position after 5 minutes rest. Baseline values are the last non-missing pre-dose assessments. Change from Baseline was defined as difference between the post-Baseline visit value and the Baseline value.

4. Change From Baseline in Pulse Rate Part 1 [Baseline, Day 1 (1, 2, 4, 6, 8, 12, 16 hours), Day 2, Day 3, Day 4, Day 5, and Day 7.]

   Pulse rate was measured in semi-supine position after 5 minutes rest. Baseline values are the last non-missing pre-dose assessments. Change from Baseline was defined as difference between the post-Baseline visit value and the Baseline value.

5. Change From Baseline in Respiratory Rate Part 1 [Baseline, Day 1 (1, 2, 4, 6, 8, 12, 16 hours), Day 2, Day 3, Day 4, Day 5, and Day 7.]

   Respiratory rate was measured in semi-supine position after 5 minutes rest. Baseline values are the last non-missing pre-dose assessments. Change from Baseline was defined as difference between the post-Baseline visit value and the Baseline value.

6. Number of Participants With Hematology Parameters Outside Reference Range Part 1 [Up to Day 7]

   Hematology parameters included hemoglobin (HGB), hematocrit (HCT), Red Blood Cell (RBC) count, White Blood Cell (WBC) count with differential (neutrophils, lymphocytes, monocytes, eosinophils, basophils), platelet count, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin concentration (MCHC). Reference range for basophil was 0.01 - 0.07*10^9/Liters (L), eosinophils 0.03 - 0.5*10^9/L, HCT 0.38 - 0.48 proportion of RBC in blood, HGB 126 - 165*gram (g)/L, lymphocytes 1.08 - 3*10^9/L, MCH 26.3 - 32.8*picogram (pg), MCHC 324 - 359*g/L, MCV 77 - 94.9*femtoliter (fL), monocytes 0.3 - 0.92*10^9/L, neutrophils 1.46 - 5.85*10^9/L, platelets 155 - 342*10^9/L, erythrocytes 4.12 - 5.74*10^12/L, leukocytes 3.19 - 8.71*10^9/L. Values below these ranges were considered as low and above these ranges were considered as high (H). Data for participants from any visit post-screening with values > reference range high and < reference range low are report.

7. Number of Participants With Clinical Chemistry Parameters Outside Reference Range [Up to Day 7]

   Clinical chemistry parameters with reference range were albumin 35-52*g/L, Alkaline phosphatase (ALP) 30-120*International units/L (IU/L), Alanine aminotransferase (ALT) 0-50 * IU/L, Aspartate aminotransferase (AST) 0-50*IU/L, direct bilirubin 0-3.4* micromoles/L (µmol/L), bilirubin 5-21*µmol/L, calcium 2.2-2.65* millimoles/L (mmol/L), cholesterol 0-5.19* mmol/L, creatinine 59-104* µmol/L, C-reactive protein (CRP) 0-5*milligram (mg)/L,Gamma Glutamyl Transferase (GGT) 4.1-5.9*mmol/L, high density lipoproteins (HDL) cholesterol 0.99-2.32*mmol/L, potassium 3.5-5.1*mmol/L, low density lipoproteins (LDL) cholesterol 0-3.3*mmol/L, protein 66-83*g/L, sodium 136-146 * mmol/L, triglycerides 0-2.25 * mmol/L, glucose 4.1-5.9*mmol/L, and urea 2.8-7.2*mmol/L. Values below these ranges were considered as low and above these ranges were considered as high. Data for participants from any visit post-screening with values > reference range high and < reference range low are reported.

8. Casts, Round Epithelial Cells (REC), Squamous Epithelial Cells (SEC), Urine Erythrocytes and Urine Leukocytes at Indicated Time Points [Pre-dose Day -1 and Day 1, Day 2, Day 4 and Day 7]

   Urinalysis included microscopic examination parameters like Casts, REC, SEC, Urine erythrocytes and Urine leukocytes. Data at indicated time points were reported. Only those participants with data available at the specified data points were analyzed (represented by n=X in category titles). NA indicates standard deviation could not be calculated as only 1 participant was analyzed at the given time point.

9. Ketones and Urine Glucose at Indicated Time Points [Pre-dose Day -1 and Day 1, Day 2, Day 4 and Day 7]

   Urinalysis included parameters like ketones and urine glucose. Data at indicated time points were reported.

10. Occult Blood at Indicated Time Points [Pre-dose Day -1 and Day 1, Day 2, Day 4 and Day 7]

    Urinalysis included parameter like Occult blood. Data at indicated time points were reported.

11. Urine Protein at Indicated Time Points [Pre-dose Day -1 and Day 1, Day 2, Day 4 and Day 7]

    Urinalysis included parameter like Urine protein. Data at indicated time points were reported.

12. Specific Gravity at Indicated Time Points [Pre-dose Day -1 and Day 1, Day 2, Day 4 and Day 7]

    Urinalysis included parameter like specific gravity. Urinary specific gravity is a measure of the concentration of solutes in the urine. It measures the ratio of urine density compared with water density and provides information on the kidney's ability to concentrate urine.

13. Urine Potential of Hydrogen (pH) at Indicated Time Points [Pre-dose Day -1 and Day 1, Day 2, Day 4 and Day 7]

    Urinalysis parameters included urine pH. pH is calculated on a scale of 0 to 14, values on the scale refer to the degree of alkalinity or acidity. A pH of 7 is neutral. A pH less than 7 is acidic, and a pH greater than 7 is basic. Normal urine has a slightly acid pH (5.0 - 6.0).

14. Number of Participants With Abnormal Electrocardiograms (ECG) Findings Worst Case Post-Baseline [Up to Day 32]

    Single measurements of 12-lead ECGs were obtained after 10 minutes of rest in a semi-supine position for the participant. Participants with abnormal ECG findings that are clinically not significant (NCS) and clinically significant (CS) data has been presented here. The data of worst case post-Baseline is presented here.

Secondary Outcome Measures

1. Maximum Observed Drug Concentration (Cmax) of GSK1795091 for Part 1 [Pre-dose, 5 minutes, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, and 144 hours post-dose]

   Blood samples were collected at indicated time points. The Pharmacokinetic (PK) parameters were calculated for each participant using a non-compartmental method. All participants for whom, at least, one valid and evaluable pharmacokinetic parameter (AUC or Cmax) was derived were included in PK Parameter Population. Only those participants with data available at the specified data points were analyzed.

2. Time of Occurrence of Cmax (Tmax) and Terminal Half Life (t1/2) of GSK1795091 for Part 1 [Pre-dose, 5 minutes, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, and 144 hours post-dose]

   Blood samples were collected at indicated time points. The PK parameters were calculated for each participant using a non-compartmental method. Only those participants with data available at the specified data points were analyzed.

3. Partial Area Under the Concentration-time Curve to Time t (AUC[0-t]), Area Under the Concentration-time Curve (AUC) From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC[0-inf]) of GSK1795091 for Part 1 [Pre-dose, 5 minutes, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, and 144 hours post-dose]

   Blood samples were collected at indicated time points. The PK parameters were calculated for each participant using a non-compartmental method. AUC (0-t) was used interchangeably with AUC to last time of quantifiable concentration (AUC[0-last]) .Only those participants with data available at the specified data points were analyzed.

4. Clearance (CL) of GSK1795091 for Part 1 [Pre-dose, 5 minutes, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, and 144 hours post-dose]

   Blood samples were collected at indicated time points. The PK parameters were calculated for each participant using a non-compartmental method. Only those participants with data available at the specified data points were analyzed.

5. Volume of Distribution of GSK1795091 for Part 1 [Pre-dose, 5 minutes, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, and 144 hours post-dose]

   Blood samples were collected at indicated time points. The PK parameters were calculated for each participant using a non-compartmental method. Only those participants with data available at the specified data points were analyzed.

6. Percentage Fold Change of Concentration of Interleukin 6 (IL-6) From Baseline for Part 1 [Baseline, 1, 2, 4, 8, 12, 16, 24, 48 and 144 hours]

   Blood samples were collected at indicated time points for the assessment of IL-6. Baseline (Day 1) was taken as the mean of the planned pre-dose measurements. Change from Baseline was defined as difference between the post-Baseline visit value and the Baseline value. Percentage fold change equals to 100*change from Baseline divided by Baseline. All participants in the "All Subjects Population" for whom valid and evaluable pharmacodynamic parameters were derived are included in Pharmacodynamic (PD) Population. Data from multiplex immunoassay has been reported.

7. Percentage Fold Change of Concentration of Tumor Necrosis Factor (TNF)-Alpha From Baseline for Part 1 [Baseline, 1, 2, 4, 8, 12, 16, 24, 48 and 144 hours]

   Blood samples were collected at indicated time points for the assessment of TNF-alpha. Baseline (Day 1) was taken as the mean of the planned pre-dose measurements. Change from Baseline was defined as difference between the post-Baseline visit value and the Baseline value. Percentage fold change equals to 100*change from Baseline divided by Baseline. Data from multiplex immunoassay has been reported. Only those participants with data available at the specified data points were analyzed (represented by n=X in category titles).

8. Percentage Fold Change of Concentration of Interferon (IFN)-Gamma From Baseline for Part 1 [Baseline, 1, 2, 4, 8, 12, 16, 24, 48 and 144 hours]

   Blood samples were collected at indicated time points for the assessment of IFN-gamma. Baseline (Day 1) was taken as the mean of the planned pre-dose measurements. Change from Baseline was defined as difference between the post-Baseline visit value and the Baseline value. Percentage fold change equals to 100*change from Baseline divided by Baseline. Data from multiplex immunoassay has been reported. Only those participants with data available at the specified data points were analyzed (represented by n=X in category titles).

9. Percentage Fold Change of Concentration of Inducible Protein (IP)-10 From Baseline for Part 1 [Baseline, 1, 2, 4, 8, 12, 16, 24, 48 and 144 hours]

   Blood samples were collected at indicated time points for the assessment of IP-10. Baseline (Day 1) was taken as the mean of the planned pre-dose measurements. Change from Baseline was defined as difference between the post-Baseline visit value and the Baseline value. Percentage fold change equals to 100*change from Baseline divided by Baseline.

10. Percentage Fold Change of Concentration of Monocyte Chemotactic Protein 1 (MCP-1) From Baseline for Part 1 [Baseline, 1, 2, 4, 8, 12, 16, 24, 48 and 144 hours]

    Blood samples were collected at indicated time points for the assessment of MCP-1. Baseline (Day 1) was taken as the mean of the planned pre-dose measurements. Change from Baseline was defined as difference between the post-Baseline visit value and the Baseline value. Percentage fold change equals to 100*change from Baseline divided by Baseline.

11. Percentage Fold Change of Colony Stimulating Factor 2 (GCSF) From Baseline for Part 1 [Baseline, 1, 2, 4, 8, 12, 16, 24, 48 and 144 hours]

    Blood samples were collected at indicated time points for the assessment of GCSF. Baseline was taken as the mean of the planned pre-dose measurements. Change from Baseline was defined as difference between the post-Baseline visit value and the Baseline value. Percentage fold change equals to 100*change from Baseline divided by Baseline.

12. Percentage Fold Change of Interleukin 1 Receptor Antagonist (IL-1Ra) From Baseline for Part 1 [Baseline, 1, 2, 4, 8, 12, 16, 24, 48 and 144 hours]

    Blood samples were collected at indicated time points for the assessment of IL-1Ra. Baseline was taken as the mean of the planned pre-dose measurements. Change from Baseline was defined as difference between the post-Baseline visit value and the Baseline value. Percentage fold change equals to 100*change from Baseline divided by Baseline.

13. Percentage Fold Change of Interleukin 10 (IL-10) From Baseline for Part 1 [Baseline, 1, 2, 4, 8, 12, 16, 24, 48 and 144 hours]

    Blood samples were collected at indicated time points for the assessment of IL-10. Baseline was taken as the mean of the planned pre-dose measurements. Change from Baseline was defined as difference between the post-Baseline visit value and the Baseline value. Percentage fold change equals to 100*change from Baseline divided by Baseline.

14. Change From Baseline in WBC Differential for Part 1 [Baseline, 4, 24 and 144 hours]

    WBC differential included Lymphocytes Count, Monocytes Count, Granulocytes Count including neutrophils and eosinophil. Baseline (Day 1) was taken as the mean of the planned pre-dose measurements. Change from Baseline was defined as difference between the post-Baseline visit value and the Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n=X in category titles).

15. Change From Baseline in CRP for Part 1 [Baseline, Days 2, 4 and 7]

    Blood samples were collected at indicated time points for the assessment of CRP. Baseline was taken as the mean of the planned pre-dose measurements. Change from Baseline was defined as difference between the post-Baseline visit value and the Baseline value.

16. Maximum Observed Drug Concentration (Cmax) of GSK1795091 for Part 2 [Pre-dose, 5 minutes, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, and 144 hours post-dose]

    Cmax assessment was planned for Part 2 after IV dose administration to healthy participants 1 or 2 Weeks after the first dose. The data for Part 2 of the study was not collected as the study was discontinued by the Sponsor prior to its scheduled start due to participant in Part 1 experienced the late occurrence of Adverse events (AEs) of unknown etiology.

17. Time of Occurrence of Cmax (Tmax) and Terminal Half Life (t1/2) of GSK1795091 for Part 2 [Pre-dose, 5 minutes, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, and 144 hours post-dose]

    Tmax and t1/2 assessments were planned for Part 2 after IV dose administration to healthy participants 1 or 2 Weeks after the first dose. The data for Part 2 of the study was not collected as the study was discontinued by the Sponsor prior to its scheduled start due to participant in Part 1 experienced the late occurrence of AEs of unknown etiology.

18. Partial Area Under the Concentration-time Curve to Time = t (AUC[0-t]), Area Under the Concentration-time Curve (AUC) From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC[0-inf]) of GSK1795091 for Part 2 [Pre-dose, 5 minutes, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, and 144 hours post-dose]

    AUC (0-t) and AUC (0-inf) assessments were planned for Part 2 after IV dose administration to healthy participants 1 or 2 Weeks after the first dose. The data for Part 2 of the study was not collected as the study was discontinued by the Sponsor prior to its scheduled start due to participant in Part 1 experienced the late occurrence of AEs of unknown etiology.

19. Area Under the Concentration-time Curve (AUC) Time Curve for a Dosing Interval (AUC[0-tau]), AUC (0-last) of GSK1795091 for Part 2 [Pre-dose, 5 minutes, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, and 144 hours post-dose]

    AUC (0-tau) and AUC (0-last) assessments were planned for Part 2 after IV dose administration to healthy participants 1 or 2 Weeks after the first dose. The data for Part 2 of the study was not collected as the study was discontinued by the Sponsor prior to its scheduled start due to participant in Part 1 experienced the late occurrence of AEs of unknown etiology.

20. Clearance (CL) of GSK1795091 for Part 2 [Pre-dose, 5 minutes, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, and 144 hours post-dose]

    CL assessment was planned for Part 2 after IV dose administration to healthy participants 1 or 2 Weeks after the first dose. The data for Part 2 of the study was not collected as the study was discontinued by the Sponsor prior to its scheduled start due to participant in Part 1 experienced the late occurrence of AEs of unknown etiology.

21. Volume of Distribution of GSK1795091 for Part 2 [Pre-dose, 5 minutes, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, and 144 hours post-dose]

    Volume of distribution assessment was planned for Part 2 after IV dose administration to healthy participants 1 or 2 Weeks after the first dose. The data for Part 2 of the study was not collected as the study was discontinued by the Sponsor prior to its scheduled start due to participant in Part 1 experienced the late occurrence of AEs of unknown etiology.

22. Accumulation Ratio of GSK1795091 for Part 2 [Pre-dose, 5 minutes, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, and 144 hours post-dose]

    Accumulation ratio assessment was planned for Part 2 after IV dose administration to healthy participants 1 or 2 Weeks after the first dose. The data for Part 2 of the study was not collected as the study was discontinued by the Sponsor prior to its scheduled start due to participant in Part 1 experienced the late occurrence of AEs of unknown etiology.

23. Time Invariance of GSK1795091 for Part 2 [Pre-dose, 5 minutes, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, and 144 hours post-dose]

    Time invariance assessment was planned for Part 2 after IV dose administration to healthy participants 1 or 2 Weeks after the first dose. The data for Part 2 of the study was not collected as the study was discontinued by the Sponsor prior to its scheduled start due to participant in Part 1 experienced the late occurrence of AEs of unknown etiology.

24. Percentage Fold Change of Concentration of Interleukin 6 (IL-6) From Baseline for Part 2 [Baseline, 1, 2, 4, 8, 12, 16, 24, 48 and 144 hours]

    IL-6 assessment was planned for Part 2 after IV dose administration to healthy participants 1 or 2 Weeks after the first dose. The data for Part 2 of the study was not collected as the study was discontinued by the Sponsor prior to its scheduled start due to participant in Part 1 experienced the late occurrence of AEs of unknown etiology.

25. Percentage Fold Change of Concentration of TNF-alpha From Baseline for Part 2 [Baseline, 1, 2, 4, 8, 12, 16, 24, 48 and 144 hours]

    TNF-alpha assessment was planned for Part 2 after IV dose administration to healthy participants 1 or 2 Weeks after the first dose. The data for Part 2 of the study was not collected as the study was discontinued by the Sponsor prior to its scheduled start due to participant in Part 1 experienced the late occurrence of AEs of unknown etiology.

26. Percentage Fold Change of Concentration of IFN-gamma From Baseline for Part 2 [Baseline, 1, 2, 4, 8, 12, 16, 24, 48 and 144 hours]

    IFN-gamma assessment was planned for Part 2 after IV dose administration to healthy participants 1 or 2 Weeks after the first dose. The data for Part 2 of the study was not collected as the study was discontinued by the Sponsor prior to its scheduled start due to participant in Part 1 experienced the late occurrence of AEs of unknown etiology.

27. Percentage Fold Change of Concentration of IP-10 From Baseline for Part 2 [Baseline, 1, 2, 4, 8, 12, 16, 24, 48 and 144 hours]

    IP-10 assessment was planned for Part 2 after IV dose administration to healthy participants 1 or 2 Weeks after the first dose. The data for Part 2 of the study was not collected as the study was discontinued by the Sponsor prior to its scheduled start due to participant in Part 1 experienced the late occurrence of AEs of unknown etiology.

28. Percentage Fold Change of Concentration of MCP-1 From Baseline for Part 2 [Baseline, 1, 2, 4, 8, 12, 16, 24, 48 and 144 hours]

    MCP-1 assessment was planned for Part 2 after IV dose administration to healthy participants 1 or 2 Weeks after the first dose. The data for Part 2 of the study was not collected as the study was discontinued by the Sponsor prior to its scheduled start due to participant in Part 1 experienced the late occurrence of AEs of unknown etiology.

29. Percentage Fold Change of Concentration of GCSF From Baseline for Part 2 [Baseline, 1, 2, 4, 8, 12, 16, 24, 48 and 144 hours]

    GCSF assessment was planned for Part 2 after IV dose administration to healthy participants 1 or 2 Weeks after the first dose. The data for Part 2 of the study was not collected as the study was discontinued by the Sponsor prior to its scheduled start due to participant in Part 1 experienced the late occurrence of AEs of unknown etiology.

30. Percentage Fold Change of Concentration of IL-1Ra From Baseline for Part 2 [Baseline, 1, 2, 4, 8, 12, 16, 24, 48 and 144 hours]

    IL-1Ra assessment was planned for Part 2 after IV dose administration to healthy participants 1 or 2 Weeks after the first dose. The data for Part 2 of the study was not collected as the study was discontinued by the Sponsor prior to its scheduled start due to participant in Part 1 experienced the late occurrence of AEs of unknown etiology.

31. Percentage Fold Change of Concentration of IL-10 From Baseline for Part 2 [Baseline, 1, 2, 4, 8, 12, 16, 24, 48 and 144 hours]

    IL-10 assessment was planned for Part 2 after IV dose administration to healthy participants 1 or 2 Weeks after the first dose. The data for Part 2 of the study was not collected as the study was discontinued by the Sponsor prior to its scheduled start due to participant in Part 1 experienced the late occurrence of AEs of unknown etiology.

32. Change From Baseline in WBC Differential for Part 2 [Baseline, 2, 24 and 144 hours]

    WBC differential assessment was planned for Part 2 after IV dose administration to healthy participants 1 or 2 Weeks after the first dose. The data for Part 2 of the study was not collected as the study was discontinued by the Sponsor prior to its scheduled start due to participant in Part 1 experienced the late occurrence of AEs of unknown etiology.

33. Number of Participants With Urinalysis Parameters Outside Reference Range for Part 2 [Up to Day 7]

    Urinalysis as part of safety assessment was planned for Part 2 after IV dose administration to healthy participants 1 or 2 Weeks after the first dose. The data for Part 2 of the study was not collected as the study was discontinued by the Sponsor prior to its scheduled start due to participant in Part 1 experienced the late occurrence of AEs of unknown etiology.

34. Number of Participants With Hematology Parameters Outside Reference Range in Part 2 [Up to Day 7]

    Hematology as part of safety assessment was planned for Part 2 after IV dose administration to healthy participants 1 or 2 Weeks after the first dose. The data for Part 2 of the study was not collected as the study was discontinued by the Sponsor prior to its scheduled start due to participant in Part 1 experienced the late occurrence of AEs of unknown etiology.

35. Number of Participants With Clinical Chemistry Parameters Outside Reference Range in Part 2 [Up to Day 7]

    Clinical chemistry as part of safety assessment was planned for Part 2 after IV dose administration to healthy participants 1 or 2 Weeks after the first dose. The data for Part 2 of the study was not collected as the study was discontinued by the Sponsor prior to its scheduled start due to participant in Part 1 experienced the late occurrence of AEs of unknown etiology.

36. Change From Baseline in CRP for Part 2 [Baseline and Pre-dose, 1, 2, 4, 8, 12, 16, 24, and 48 hours post dose]

    CRP assessment was planned for Part 2 after IV dose administration to healthy participants 1 or 2 Weeks after the first dose. The data for Part 2 of the study was not collected as the study was discontinued by the Sponsor prior to its scheduled start due to participant in Part 1 experienced the late occurrence of AEs of unknown etiology.

37. Change From Baseline in Body Temperature for Part 2 [Baseline and up to Day 7]

    Body temperature was planned to be measured in Part 2 after IV dose administration to healthy participants 1 or 2 Weeks after the first dose. The data for Part 2 of the study was not collected as the study was discontinued by the Sponsor prior to its scheduled start due to participant in Part 1 experienced the late occurrence of AEs of unknown etiology.

38. Change From Baseline in SBP and DBP for Part 2 [Baseline and up to Day 7]

    SBP and DBP was planned to be measured in Part 2 after IV dose administration to healthy participants 1 or 2 Weeks after the first dose. The data for Part 2 of the study was not collected as the study was discontinued by the Sponsor prior to its scheduled start due to participant in Part 1 experienced the late occurrence of AEs of unknown etiology.

39. Change From Baseline in Respiratory Rate for Part 2 [Baseline and up to Day 7]

    Respiratory rate was planned to be measured in Part 2 after IV dose administration to healthy participants 1 or 2 Weeks after the first dose. The data for Part 2 of the study was not collected as the study was discontinued by the Sponsor prior to its scheduled start due to participant in Part 1 experienced the late occurrence of AEs of unknown etiology.

40. Change From Baseline in Pulse Rate for Part 2 [Baseline and up to Day 7]

    Pulse rate was planned to be measured in Part 2 after IV dose administration to healthy participants 1 or 2 Weeks after the first dose. Baseline (Day 1) was taken as the mean of the planned pre-dose measurements. Change from Baseline was defined as difference between the post-Baseline visit value and the Baseline value. The data for Part 2 of the study was not collected as the study was discontinued by the Sponsor prior to its scheduled start due to participant in Part 1 experienced the late occurrence of AEs of unknown etiology.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 50 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Between 18 and 50 years of age inclusive, at the time of signing the informed consent.

• Healthy as determined by the investigator or medically qualified designee based on a medical evaluation including medical history, physical examination, laboratory tests, vital signs and 12-lead ECG. (A subject with a clinically insignificant abnormality or laboratory parameter(s) may be included only if the Investigator documents that the finding is unlikely to represent a safety risk and will not interfere with the study procedures.)

• Body weight 55-95 kilogram (kg) and body mass index within the range 19-30 kg/meter (m)^2 (inclusive).

• Male or Female of non-childbearing potential:

Males: Male subjects with female partners of child bearing potential must comply with the pre specified contraception requirements.

Females: A female subject is eligible to participate if she is not pregnant (as confirmed by a negative serum or urine human chorionic gonadotropin test), not lactating, and is either of non-reproductive potential or reproductive potential. If of reproductive potential, then the subject should agree to follow one of the options listed per GSK Modified List of Highly Effective Methods for Avoiding Pregnancy in Females of Reproductive Potential from 30 days prior to the first dose and until 30 days after the last dose of study medication The Investigator is responsible for ensuring that subjects understand how to properly use these methods of contraception

• Capable of giving signed informed consent

Exclusion Criteria:

• History of any significant medical condition (e.g. cardiac, pulmonary, metabolic, renal, gastrointestinal, rheumatological, etc.)

• History of frequent (>1 per week) headache or myalgia, asthma, syncope.

• History of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome).

• Alanine aminotransferase (ALT) and bilirubin >1.1×upper limit of normal (ULN; isolated bilirubin >1.5×ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).

• Vital signs:

Systolic blood pressure (SBP) <90 and >140 milliliter of mercury (mmHg); diastolic BP <50 and >90 mmHg; heart rate (HR) <50 and >90 beats per minute (bpm); temperature >37.5 degree Celsius

• Clinically significant ECG abnormality and/or HR < 50 and >90 bpm; PR interval >220 milliseconds (msec); QRS duration >120 msec; and QTcF > 450 msec

• Anticipated requirement for any prescription medication during the study

• History of regular alcohol consumption within 6 months of the study averaging a weekly intake of >14 drinks for males or >7 drinks for females or inability to abstain from alcohol from 1 day prior to the inpatient period of the study until discharge (one drink is equivalent to 8 grams of alcohol: 200 milliliter [mL] of beer, 100 mL of wine or 1 measure (25 mL) of spirits)

• Urinary cotinine levels indicative of smoking or history or regular use of tobacco or nicotine-containing products within 2 months prior to screening or inability to abstain from smoking during the study

• 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

• Presence of hepatitis B surface antigen, positive hepatitis C antibody test result at screening or within 3 months prior to first dose of study treatment. Subjects with positive Hepatitis C antibody due to prior resolved disease can be enrolled, only if a confirmatory negative Hepatitis C ribonucleic acid polymerase chain reaction test is obtained.

• A positive pre-study drug/alcohol screen.

• A positive test for human immunodeficiency antivirus antibody.

• Donation of blood or blood products in excess of 500 mL within a 56-day period.

• The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first visit (Day -2) in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).

• Exposure to more than four new chemical entities within 12 months prior to the first visit (Day -2).

• Exposure to GSK1795091 in a previous cohort of this study.

• Subject is unable to refrain from taking non-prescription drugs (including vitamins and dietary or herbal supplements), within 7 days prior to the first dose of study medication until completion of the follow-up visit, unless in the opinion of the investigator and sponsor, the medication will not interfere with the study.

• Subject is able to understand and communicate in German/or native language of the site. Subject, or close relative of the subject, is the investigator or a sub-investigator, research assistant, pharmacist, study coordinator, or other staff directly involved with the conduct of the study at that site

• Vulnerable subjects (eg subjects kept in detention)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Berlin		Germany	14050

Sponsors and Collaborators

• GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

• Study Protocol - Apr 12, 2017
• Statistical Analysis Plan - Nov 19, 2017

More Information

Publications

• Hug BA, Matheny CJ, Burns O, Struemper H, Wang X, Washburn ML. Safety, Pharmacokinetics, and Pharmacodynamics of the TLR4 Agonist GSK1795091 in Healthy Individuals: Results from a Randomized, Double-blind, Placebo-controlled, Ascending Dose Study. Clin Ther. 2020 Aug;42(8):1519-1534.e33. doi: 10.1016/j.clinthera.2020.05.022. Epub 2020 Jul 30.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT02798978
• Other Study ID Numbers: 204685; 2016-000759-28
• First Posted: Jun 14, 2016
• Last Update Posted: Nov 27, 2020
• Last Verified: Nov 1, 2020

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by GlaxoSmithKline: pharmacokinetics; TLR4 agonist; cancer; tolerability; GSK1795091; pharmacodynamics; safety

Study Results

Participant Flow

Recruitment Details	This study was planned to be conducted in 2-parts, however Part 2 was discontinued by the Sponsor prior to its scheduled start. Part 1 was single-dose escalation, sequential group evaluation of intravenously administered GSK1795091 to evaluate the safety and tolerability in healthy participants.
Pre-assignment Detail	Forty two participants were randomized in Part 1 of which 2 did not receive dose due to abnormal findings during pre-dose examination. Participants were randomized in ratio of 3:1 to receive GSK1795091 or matching placebo.

Arm/Group Title	Part 1: Placebo	Part 1: GSK1795091 7 ng	Part 1: GSK1795091 21 ng	Part 1: GSK1795091 60 ng	Part 1: GSK1795091 Repeated 60 ng	Part 1: GSK1795091 100 ng	All Participants in Part 2
Arm/Group Description	Participants in Part 1 were randomized to receive intravenous (IV) matching Placebo of GSK1795091. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 7 nanogram (ng). Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 21 ng. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 60 ng. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV repeat dose of GSK1795091 60 ng as the study was restarted. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 100 ng. Participants were observed inpatient until discharge on Day 5.	In part 2, two doses GSK1795091 determined by results from Part 1 were planned in parallel group evaluation. Part 2 was discontinued by the Sponsor prior to its scheduled start and no participants were enrolled.
Period Title: Part 1 (30 Days)
STARTED	10	6	6	6	6	6	0
COMPLETED	10	6	6	6	6	6	0
NOT COMPLETED	0	0	0	0	0	0	0
Period Title: Part 1 (30 Days)
STARTED	0	0	0	0	0	0	0
COMPLETED	0	0	0	0	0	0	0
NOT COMPLETED	0	0	0	0	0	0	0

Baseline Characteristics

Arm/Group Title	Part 1: Placebo	Part 1: GSK1795091 7 ng	Part 1: GSK1795091 21 ng	Part 1: GSK1795091 60 ng	Part 1: GSK1795091 Repeated 60 ng	Part 1: GSK1795091 100 ng	All Participants in Part 2	Total
Arm/Group Description	Participants in Part 1 were randomized to receive intravenous (IV) matching Placebo of GSK1795091. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 7 nanogram (ng). Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 21 ng. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 60 ng. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV repeat dose of GSK1795091 60 ng as the study was restarted. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 100 ng. Participants were observed inpatient until discharge on Day 5.	In part 2, two doses GSK1795091 determined by results from Part 1 were planned in parallel group evaluation. Part 2 was discontinued by the Sponsor prior to its scheduled start and no participants were enrolled.	Total of all reporting groups
Overall Participants	10	6	6	6	6	6	0	40
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	35.2 (8.42)	30.2 (6.62)	40.5 (7.64)	39.7 (7.47)	43.3 (8.43)	38.3 (6.02)	37.6 (8.21)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%	0 0%	1 16.7%	0 0%	1 Infinity
Male	10 100%	6 100%	6 100%	6 100%	5 83.3%	6 100%	39 Infinity
Race/Ethnicity, Customized (Count of Participants)
Black or African American	1 10%	0 0%	0 0%	0 0%	1 16.7%	0 0%	2 Infinity
White/Caucasian/European Heritage	9 90%	6 100%	6 100%	6 100%	5 83.3%	6 100%	38 Infinity

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Non-serious Adverse Events (AE) and Serious Adverse Events (SAE)
Description	An AE is any untoward medical occurrence in a clinical investigation 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, any other situation according to medical or scientific judgment or events associated with liver injury and impaired liver function were categorized as SAE. All participants enrolled into the study who have received a dose of study medication (GSK1795091 or placebo) were included in the All Subjects Population. Participants with non-serious AEs (5 percentage threshold) and SAEs has been reported.
Time Frame	Up to Day 32

Outcome Measure Data

Analysis Population Description

All Subjects Population.

Arm/Group Title	Part 1: Placebo	Part 1: GSK1795091 7 ng	Part 1: GSK1795091 21 ng	Part 1: GSK1795091 60 ng	Part 1: GSK1795091 Repeated 60 ng	Part 1: GSK1795091 100 ng
Arm/Group Description	Participants in Part 1 were randomized to receive IV matching Placebo of GSK1795091. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 7 ng. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 21 ng. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 60 ng. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV repeat dose of GSK1795091 60 ng as the study was restarted. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 100 ng. Participants were observed inpatient until discharge on Day 5.
Measure Participants	10	6	6	6	6	6
Any SAE	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Non-SAE (>= 5%)	0 0%	2 33.3%	0 0%	5 83.3%	3 50%	5 83.3%

2. Primary Outcome

Title	Change From Baseline in Body Temperature Part 1
Description	Body temperature was measured in semi-supine position after 5 minutes rest. Baseline values are the last non-missing pre-dose assessments. Change from Baseline was defined as difference between the post-Baseline visit value and the Baseline value.
Time Frame	Baseline, Day 1 (1, 2, 4, 6, 8, 12, 16 hours), Day 2, Day 3, Day 4, Day 5, and Day 7.

Outcome Measure Data

Analysis Population Description

All Subjects Population.

Arm/Group Title	Part 1: Placebo	Part 1: GSK1795091 7 ng	Part 1: GSK1795091 21 ng	Part 1: GSK1795091 60 ng	Part 1: GSK1795091 Repeated 60 ng	Part 1: GSK1795091 100 ng
Arm/Group Description	Participants in Part 1 were randomized to receive IV matching Placebo of GSK1795091. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 7 ng. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 21 ng. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 60 ng. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV repeat dose of GSK1795091 60 ng as the study was restarted. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 100 ng. Participants were observed inpatient until discharge on Day 5.
Measure Participants	10	6	6	6	6	6
Day 1, 1 hour	0.14 (0.084)	0.17 (0.163)	0.08 (0.264)	0.15 (0.187)	0.15 (0.281)	0.17 (0.327)
Day 1, 2 hour	0.17 (0.095)	0.23 (0.163)	0.32 (0.232)	0.68 (0.354)	0.40 (0.179)	0.87 (0.367)
Day 1, 4 hour	0.26 (0.196)	0.42 (0.147)	0.55 (0.389)	0.98 (0.556)	0.63 (0.383)	1.25 (0.295)
Day 1, 6 hour	0.43 (0.206)	0.53 (0.301)	0.45 (0.464)	0.82 (0.665)	0.38 (0.483)	0.93 (0.163)
Day 1, 8 hour	0.41 (0.197)	0.53 (0.273)	0.43 (0.301)	0.63 (0.432)	0.57 (0.258)	0.75 (0.389)
Day 1, 12 hour	0.14 (0.255)	0.18 (0.337)	0.28 (0.397)	0.28 (0.397)	0.23 (0.242)	0.67 (0.294)
Day 1, 16 hour	0.03 (0.258)	0.02 (0.223)	-0.08 (0.319)	0.03 (0.175)	0.03 (0.225)	0.32 (0.349)
Day 2	0.06 (0.190)	-0.02 (0.172)	-0.05 (0.226)	0.12 (0.147)	-0.08 (0.117)	0.13 (0.186)
Day 3	-0.10 (0.221)	0.07 (0.207)	-0.17 (0.225)	0.10 (0.179)	-0.13 (0.250)	-0.08 (0.204)
Day 4	0.01 (0.197)	0.25 (0.259)	-0.15 (0.217)	0.05 (0.266)	0.02 (0.223)	-0.12 (0.204)
Day 5	0.14 (0.178)	0.22 (0.147)	-0.12 (0.194)	0.17 (0.273)	-0.13 (0.250)	0.13 (0.234)
Day 7	0.02 (0.199)	0.12 (0.204)	-0.13 (0.314)	0.08 (0.354)	-0.20 (0.415)	0.10 (0.228)

3. Primary Outcome

Title	Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) Part 1
Description	Systolic and diastolic BP was measured in semi-supine position after 5 minutes rest. Baseline values are the last non-missing pre-dose assessments. Change from Baseline was defined as difference between the post-Baseline visit value and the Baseline value.
Time Frame	Baseline, Day 1 (1, 2, 4, 6, 8, 12, 16 hours), Day 2, Day 3, Day 4, Day 5, and Day 7.

Outcome Measure Data

Analysis Population Description

All Subjects Population.

Arm/Group Title	Part 1: Placebo	Part 1: GSK1795091 7 ng	Part 1: GSK1795091 21 ng	Part 1: GSK1795091 60 ng	Part 1: GSK1795091 Repeated 60 ng	Part 1: GSK1795091 100 ng
Arm/Group Description	Participants in Part 1 were randomized to receive IV matching Placebo of GSK1795091. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 7 ng. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 21 ng. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 60 ng. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV repeat dose of GSK1795091 60 ng as the study was restarted. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 100 ng. Participants were observed inpatient until discharge on Day 5.
Measure Participants	10	6	6	6	6	6
DBP, Day 1, 1 hour	-2.1 (6.14)	-3.8 (2.79)	-2.3 (5.50)	-1.3 (4.27)	-3.2 (5.23)	-3.3 (4.18)
DBP, Day 1, 2 hour	-4.3 (4.00)	-5.0 (1.26)	-5.0 (10.06)	-6.5 (2.43)	-4.8 (3.43)	-7.0 (8.20)
DBP, Day 1, 4 hour	-1.9 (4.77)	-3.8 (3.54)	-3.7 (5.05)	-3.7 (5.82)	-4.5 (4.14)	-4.2 (4.88)
DBP, Day 1, 6 hour	-0.5 (4.86)	-6.0 (4.86)	-3.5 (6.09)	-5.3 (8.21)	-0.8 (6.34)	-7.5 (6.38)
DBP, Day 1, 8 hour	0.9 (5.17)	-0.5 (2.95)	-2.3 (5.47)	-4.3 (10.73)	-0.8 (5.23)	-6.8 (6.85)
DBP, Day 1, 12 hour	-2.2 (6.01)	-0.3 (6.25)	-2.7 (11.17)	-2.8 (5.27)	-4.3 (7.03)	-2.0 (8.32)
DBP, Day 1, 16 hour	-3.2 (6.00)	-5.5 (8.87)	-5.8 (15.22)	-6.2 (5.88)	-3.8 (5.04)	-2.7 (10.13)
DBP, Day 2	0.0 (5.40)	1.0 (6.10)	-5.3 (8.80)	-1.0 (6.66)	1.3 (7.87)	0.7 (7.00)
DBP, Day 3	0.1 (6.30)	-1.3 (5.39)	-5.0 (8.99)	4.3 (10.89)	1.0 (6.51)	0.8 (7.08)
DBP, Day 4	2.6 (9.38)	0.7 (8.41)	-6.2 (11.29)	-2.2 (9.62)	-1.0 (4.10)	-1.0 (6.23)
DBP, Day 5	2.4 (5.02)	4.2 (4.54)	-1.2 (10.25)	1.5 (10.45)	1.5 (2.07)	2.5 (6.06)
DBP, Day 7	0.9 (7.03)	3.7 (6.71)	-1.8 (7.86)	4.7 (9.22)	1.3 (6.31)	3.2 (9.43)
SBP, Day 1, 1 hour	6.5 (5.78)	4.7 (8.89)	1.5 (9.05)	8.8 (8.16)	3.3 (6.12)	-1.3 (14.60)
SBP, Day 1, 2 hour	-2.0 (6.53)	-1.2 (5.56)	-1.2 (11.23)	-3.7 (8.52)	1.2 (7.08)	0.8 (6.05)
SBP, Day 1, 4 hour	-1.6 (4.25)	-1.0 (7.56)	-4.2 (11.99)	0.3 (6.35)	1.7 (8.55)	1.2 (3.37)
SBP, Day 1, 6 hour	5.0 (8.65)	4.2 (4.31)	2.2 (11.70)	1.8 (10.46)	7.5 (9.35)	3.2 (6.46)
SBP, Day 1, 8 hour	0.7 (8.04)	2.3 (5.68)	0.8 (17.78)	-2.7 (10.98)	2.5 (6.25)	-2.3 (4.72)
SBP, Day 1, 12 hour	3.9 (11.56)	2.3 (4.32)	6.0 (19.76)	6.2 (5.85)	6.2 (9.68)	2.0 (7.21)
SBP, Day 1, 16 hour	-1.8 (6.16)	-6.8 (6.43)	-7.2 (22.51)	-6.8 (8.11)	-1.0 (14.10)	0.8 (13.29)
SBP, Day 2	-3.2 (7.15)	-1.8 (3.60)	-5.0 (17.44)	-2.3 (11.54)	-0.7 (5.16)	2.2 (6.85)
SBP, Day 3	-2.0 (10.09)	-1.3 (5.89)	-7.8 (15.94)	5.0 (8.39)	1.8 (5.12)	1.0 (8.81)
SBP, Day 4	0.7 (6.50)	-1.7 (8.38)	-8.2 (19.86)	-1.8 (12.88)	-1.7 (5.85)	-0.3 (2.66)
SBP, Day 5	4.2 (4.69)	1.5 (3.08)	-2.5 (17.76)	9.5 (13.43)	5.0 (4.65)	4.0 (5.37)
SBP, Day 7	-0.1 (6.81)	5.3 (8.91)	-4.3 (14.96)	2.3 (10.78)	1.5 (11.50)	5.2 (7.83)

4. Primary Outcome

Title	Change From Baseline in Pulse Rate Part 1
Description	Pulse rate was measured in semi-supine position after 5 minutes rest. Baseline values are the last non-missing pre-dose assessments. Change from Baseline was defined as difference between the post-Baseline visit value and the Baseline value.
Time Frame	Baseline, Day 1 (1, 2, 4, 6, 8, 12, 16 hours), Day 2, Day 3, Day 4, Day 5, and Day 7.

Outcome Measure Data

Analysis Population Description

All Subjects Population.

Arm/Group Title	Part 1: Placebo	Part 1: GSK1795091 7 ng	Part 1: GSK1795091 21 ng	Part 1: GSK1795091 60 ng	Part 1: GSK1795091 Repeated 60 ng	Part 1: GSK1795091 100 ng
Arm/Group Description	Participants in Part 1 were randomized to receive IV matching Placebo of GSK1795091. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 7 ng. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 21 ng. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 60 ng. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV repeat dose of GSK1795091 60 ng as the study was restarted. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 100 ng. Participants were observed inpatient until discharge on Day 5.
Measure Participants	10	6	6	6	6	6
Day 1, 1 hour	8.1 (6.92)	8.2 (3.31)	11.8 (7.65)	16.7 (7.66)	12.0 (5.10)	10.2 (4.88)
Day 1, 2 hour	5.9 (5.36)	8.2 (8.57)	11.3 (11.74)	17.5 (8.60)	14.8 (9.45)	14.3 (7.45)
Day 1, 4 hour	5.0 (7.67)	2.8 (2.99)	11.7 (15.12)	17.8 (20.22)	17.3 (9.79)	20.8 (5.42)
Day 1, 6 hour	8.7 (6.73)	8.7 (3.98)	10.8 (13.12)	15.7 (17.07)	17.7 (7.37)	15.7 (5.09)
Day 1, 8 hour	3.2 (6.49)	1.7 (3.20)	4.7 (6.15)	4.7 (8.87)	8.2 (5.74)	6.3 (5.35)
Day 1, 12 hour	4.6 (8.45)	4.7 (5.99)	5.2 (15.48)	7.2 (4.07)	10.5 (4.59)	9.0 (6.57)
Day 1, 16 hour	-1.9 (5.55)	-2.0 (4.94)	-0.8 (19.77)	-0.7 (5.61)	3.2 (2.64)	2.8 (5.56)
Day 2	0.3 (4.37)	-0.3 (3.78)	1.0 (7.64)	4.3 (6.12)	0.5 (4.04)	1.7 (8.16)
Day 3	1.4 (3.27)	5.5 (4.37)	-1.3 (12.71)	7.0 (7.62)	2.0 (3.16)	-1.2 (5.71)
Day 4	3.2 (7.69)	4.8 (7.60)	-1.3 (13.84)	4.5 (4.97)	2.2 (6.21)	-2.3 (3.83)
Day 5	7.3 (8.58)	6.3 (6.41)	2.2 (14.69)	4.5 (5.24)	4.5 (7.56)	2.7 (3.01)
Day 7	7.4 (5.50)	7.0 (4.43)	1.7 (10.46)	3.8 (7.19)	6.7 (13.41)	3.8 (5.19)

5. Primary Outcome

Title	Change From Baseline in Respiratory Rate Part 1
Description	Respiratory rate was measured in semi-supine position after 5 minutes rest. Baseline values are the last non-missing pre-dose assessments. Change from Baseline was defined as difference between the post-Baseline visit value and the Baseline value.
Time Frame	Baseline, Day 1 (1, 2, 4, 6, 8, 12, 16 hours), Day 2, Day 3, Day 4, Day 5, and Day 7.

Outcome Measure Data

Analysis Population Description

All Subjects Population.

Arm/Group Title	Part 1: Placebo	Part 1: GSK1795091 7 ng	Part 1: GSK1795091 21 ng	Part 1: GSK1795091 60 ng	Part 1: GSK1795091 Repeated 60 ng	Part 1: GSK1795091 100 ng
Arm/Group Description	Participants in Part 1 were randomized to receive IV matching Placebo of GSK1795091. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 7 nanogram (ng). Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 21 ng. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 60 ng. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV repeat dose of GSK1795091 60 ng as the study was restarted. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 100 ng. Participants were observed inpatient until discharge on Day 5.
Measure Participants	10	6	6	6	6	6
Day 1, 1 hour	0.2 (1.03)	1.2 (0.41)	-0.2 (1.17)	1.2 (2.93)	-0.2 (1.60)	-0.2 (1.94)
Day 1, 2 hour	0.3 (1.49)	0.2 (0.75)	-0.2 (0.75)	1.3 (3.08)	1.0 (0.89)	0.2 (1.94)
Day 1, 4 hour	0.2 (1.14)	0.0 (1.79)	-0.2 (2.93)	1.0 (2.00)	1.2 (2.04)	1.5 (4.04)
Day 1, 6 hour	0.9 (2.96)	0.3 (2.34)	-0.7 (1.51)	-0.3 (2.34)	1.5 (2.74)	0.7 (3.27)
Day 1, 8 hour	1.3 (2.31)	1.0 (2.68)	-0.3 (1.97)	0.8 (4.36)	0.8 (1.72)	-0.5 (2.88)
Day 1, 12 hour	0.4 (2.37)	-0.5 (1.76)	0.0 (3.22)	0.8 (2.40)	0.8 (1.72)	0.5 (3.56)
Day 1, 16 hour	-0.4 (2.22)	-1.8 (2.14)	-1.3 (2.25)	0.0 (3.35)	0.7 (1.75)	-0.8 (2.23)
Day 2	-0.3 (1.70)	0.2 (1.60)	-0.3 (0.82)	-0.5 (2.95)	1.5 (2.17)	-0.3 (3.01)
Day 3	0.4 (1.90)	-0.3 (1.97)	0.3 (3.56)	0.3 (2.07)	1.3 (2.34)	-0.2 (2.40)
Day 4	0.6 (2.01)	-0.2 (1.72)	-0.5 (2.26)	-0.5 (2.51)	0.5 (2.07)	-0.2 (2.56)
Day 5	0.4 (0.97)	-0.7 (1.21)	0.5 (3.27)	1.5 (1.76)	0.8 (1.47)	0.3 (3.61)
Day 7	0.3 (1.89)	-0.3 (1.21)	-0.5 (1.87)	0.5 (2.07)	-0.3 (1.86)	0.5 (2.07)

6. Primary Outcome

Title	Number of Participants With Hematology Parameters Outside Reference Range Part 1
Description	Hematology parameters included hemoglobin (HGB), hematocrit (HCT), Red Blood Cell (RBC) count, White Blood Cell (WBC) count with differential (neutrophils, lymphocytes, monocytes, eosinophils, basophils), platelet count, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin concentration (MCHC). Reference range for basophil was 0.01 - 0.07*10^9/Liters (L), eosinophils 0.03 - 0.5*10^9/L, HCT 0.38 - 0.48 proportion of RBC in blood, HGB 126 - 165*gram (g)/L, lymphocytes 1.08 - 3*10^9/L, MCH 26.3 - 32.8*picogram (pg), MCHC 324 - 359*g/L, MCV 77 - 94.9*femtoliter (fL), monocytes 0.3 - 0.92*10^9/L, neutrophils 1.46 - 5.85*10^9/L, platelets 155 - 342*10^9/L, erythrocytes 4.12 - 5.74*10^12/L, leukocytes 3.19 - 8.71*10^9/L. Values below these ranges were considered as low and above these ranges were considered as high (H). Data for participants from any visit post-screening with values > reference range high and < reference range low are report.
Time Frame	Up to Day 7

Outcome Measure Data

Analysis Population Description

All Subjects Population.

Arm/Group Title	Part 1: Placebo	Part 1: GSK1795091 7 ng	Part 1: GSK1795091 21 ng	Part 1: GSK1795091 60 ng	Part 1: GSK1795091 Repeated 60 ng	Part 1: GSK1795091 100 ng
Arm/Group Description	Participants in Part 1 were randomized to receive IV matching Placebo of GSK1795091. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 7 ng. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 21 ng. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 60 ng. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV repeat dose of GSK1795091 60 ng as the study was restarted. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 100 ng. Participants were observed inpatient until discharge on Day 5.
Measure Participants	10	6	6	6	6	6
Basophil, > reference range H	0 0%	0 0%	0 0%	0 0%	0 0%	1 16.7%
Basophil, < reference range low	1 10%	0 0%	0 0%	0 0%	0 0%	0 0%
Eosinophils, > reference range H	0 0%	0 0%	2 33.3%	0 0%	0 0%	1 16.7%
Eosinophils, < reference range low	2 20%	0 0%	0 0%	0 0%	0 0%	2 33.3%
MCHC, > reference range H	1 10%	0 0%	0 0%	0 0%	0 0%	0 0%
MCHC,< reference range low	0 0%	0 0%	1 16.7%	0 0%	1 16.7%	0 0%
MCH, > reference range H	0 0%	2 33.3%	1 16.7%	0 0%	1 16.7%	1 16.7%
MCH, < reference range low	0 0%	0 0%	1 16.7%	0 0%	1 16.7%	1 16.7%
MCV, > reference range H	2 20%	1 16.7%	2 33.3%	0 0%	0 0%	0 0%
MCV, < reference range low	0 0%	0 0%	1 16.7%	0 0%	1 16.7%	0 0%
Erythrocytes, > reference range H	0 0%	0 0%	1 16.7%	0 0%	0 0%	0 0%
Erythrocytes, < reference range low	1 10%	1 16.7%	0 0%	0 0%	0 0%	0 0%
HCT,> reference range H	1 10%	0 0%	0 0%	0 0%	0 0%	0 0%
HCT, < reference range low	1 10%	1 16.7%	0 0%	1 16.7%	1 16.7%	0 0%
HGB,> reference range H	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
HGB, < reference range low	0 0%	0 0%	1 16.7%	0 0%	1 16.7%	0 0%
Leukocytes,> reference range H	1 10%	1 16.7%	5 83.3%	4 66.7%	5 83.3%	5 83.3%
Leukocytes, < reference range low	1 10%	0 0%	0 0%	2 33.3%	1 16.7%	3 50%
Lymphocytes,> reference range H	3 30%	1 16.7%	0 0%	0 0%	0 0%	0 0%
Lymphocytes, < reference range low	1 10%	3 50%	3 50%	6 100%	6 100%	6 100%
Monocytes,> reference range H	0 0%	0 0%	2 33.3%	0 0%	0 0%	0 0%
Monocytes, < reference range low	4 40%	4 66.7%	5 83.3%	6 100%	6 100%	6 100%
Neutrophils,> reference range H	0 0%	0 0%	5 83.3%	4 66.7%	5 83.3%	6 100%
Neutrophils, < reference range low	2 20%	0 0%	1 16.7%	1 16.7%	1 16.7%	3 50%
Platelets,> reference range H	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Platelets, < reference range low	1 10%	3 50%	0 0%	0 0%	1 16.7%	1 16.7%

7. Primary Outcome

Title	Number of Participants With Clinical Chemistry Parameters Outside Reference Range
Description	Clinical chemistry parameters with reference range were albumin 35-52*g/L, Alkaline phosphatase (ALP) 30-120*International units/L (IU/L), Alanine aminotransferase (ALT) 0-50 * IU/L, Aspartate aminotransferase (AST) 0-50*IU/L, direct bilirubin 0-3.4* micromoles/L (µmol/L), bilirubin 5-21*µmol/L, calcium 2.2-2.65* millimoles/L (mmol/L), cholesterol 0-5.19* mmol/L, creatinine 59-104* µmol/L, C-reactive protein (CRP) 0-5*milligram (mg)/L,Gamma Glutamyl Transferase (GGT) 4.1-5.9*mmol/L, high density lipoproteins (HDL) cholesterol 0.99-2.32*mmol/L, potassium 3.5-5.1*mmol/L, low density lipoproteins (LDL) cholesterol 0-3.3*mmol/L, protein 66-83*g/L, sodium 136-146 * mmol/L, triglycerides 0-2.25 * mmol/L, glucose 4.1-5.9*mmol/L, and urea 2.8-7.2*mmol/L. Values below these ranges were considered as low and above these ranges were considered as high. Data for participants from any visit post-screening with values > reference range high and < reference range low are reported.
Time Frame	Up to Day 7

Outcome Measure Data

Analysis Population Description

All Subjects Population.

Arm/Group Title	Part 1: Placebo	Part 1: GSK1795091 7 ng	Part 1: GSK1795091 21 ng	Part 1: GSK1795091 60 ng	Part 1: GSK1795091 Repeated 60 ng	Part 1: GSK1795091 100 ng
Arm/Group Description	Participants in Part 1 were randomized to receive IV matching Placebo of GSK1795091. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 7 ng. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 21 ng. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 60 ng. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV repeat dose of GSK1795091 60 ng as the study was restarted. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 100 ng. Participants were observed inpatient until discharge on Day 5.
Measure Participants	10	6	6	6	6	6
ALT, > reference range H	0 0%	0 0%	2 33.3%	0 0%	1 16.7%	0 0%
ALT, < reference range low	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Albumin, > reference range H	00 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Albumin, < reference range low	0 0%	0 0%	0 0%	1 16.7%	0 0%	0 0%
ALP, > reference range H	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
ALP,< reference range low	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
AST, > reference range H	0 0%	0 0%	0 0%	1 16.7%	0 0%	0 0%
AST, < reference range low	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Bilirubin, > reference range H	2 20%	1 16.7%	0 0%	0 0%	0 0%	0 0%
Bilirubin, < reference range low	3 30%	0 0%	0 0%	1 16.7%	0 0%	0 0%
CRP, > reference range H	1 10%	0 0%	2 33.3%	4 66.7%	5 83.3%	6 100%
CRP, < reference range low	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Calcium,> reference range H	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Calcium, < reference range low	1 10%	0 0%	1 16.7%	1 16.7%	2 33.3%	2 33.3%
Creatinine,> reference range H	0 0%	0 0%	1 16.7%	0 0%	0 0%	0 0%
Creatinine, < reference range low	1 10%	0 0%	1 16.7%	0 0%	0 0%	1 16.7%
Direct Bilirubin,> reference range H	1 10%	1 16.7%	0 0%	0 0%	0 0%	0 0%
Direct Bilirubin, < reference range low	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Glucose,> reference range H	0 0%	0 0%	2 33.3%	0 0%	0 0%	0 0%
Glucose, < reference range low	0 0%	0 0%	0 0%	2 33.3%	0 0%	1 16.7%
Indirect bilirubin,> reference range H	1 10%	0 0%	0 0%	0 0%	0 0%	0 0%
Indirect bilirubin, < reference range low	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Potassium,> reference range H	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Potassium, < reference range low	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Protein,> reference range H	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Protein, < reference range low	4 40%	4 66.7%	3 50%	4 66.7%	4 66.7%	5 83.3%
Sodium,> reference range H	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Sodium, < reference range low	2 20%	2 33.3%	3 50%	2 33.3%	3 50%	3 50%
Urea,> reference range H	0 0%	1 16.7%	0 0%	0 0%	0 0%	0 0%
Urea, < reference range low	1 10%	1 16.7%	1 16.7%	1 16.7%	1 16.7%	0 0%

8. Primary Outcome

Title	Casts, Round Epithelial Cells (REC), Squamous Epithelial Cells (SEC), Urine Erythrocytes and Urine Leukocytes at Indicated Time Points
Description	Urinalysis included microscopic examination parameters like Casts, REC, SEC, Urine erythrocytes and Urine leukocytes. Data at indicated time points were reported. Only those participants with data available at the specified data points were analyzed (represented by n=X in category titles). NA indicates standard deviation could not be calculated as only 1 participant was analyzed at the given time point.
Time Frame	Pre-dose Day -1 and Day 1, Day 2, Day 4 and Day 7

Outcome Measure Data

Analysis Population Description

All Subjects Population

Arm/Group Title	Part 1: Placebo	Part 1: GSK1795091 7 ng	Part 1: GSK1795091 21 ng	Part 1: GSK1795091 60 ng	Part 1: GSK1795091 Repeated 60 ng	Part 1: GSK1795091 100 ng
Arm/Group Description	Participants in Part 1 were randomized to receive IV matching Placebo of GSK1795091. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 7 ng. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 21 ng. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 60 ng. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV repeat dose of GSK1795091 60 ng as the study was restarted. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 100 ng. Participants were observed inpatient until discharge on Day 5.
Measure Participants	10	6	6	6	6	6
Casts, Day -1 Pre-dose, n=1,0,2,1,0,1	0.0 (NA)	0.0 (0.0)	0.0 (NA)	0.0 (NA)
Casts, Day 1, Pre-dose, n=3,1,2,0,0,2	0.0 (0.0)	0.0 (NA)	0.0 (0.0)	0.0 (0.0)
Casts, Day 2, n=1,0,3,1,1,2	0.0 (NA)	0.0 (0.0)	0.0 (NA)	0.0 (NA)	0.0 (0.0)
Casts, Day 4, n=3,0,1,2,0,0	0.0 (0.0)	0.0 (NA)	0.0 (0.0)
Casts, Day 7, n=4,0,2,2,0,0	0.0 (0.0)	0.0 (0.0)	0.0 (0.0)
REC, Day -1 Pre-dose, n=1,0,2,1,0,1	0.0 (NA)	0.0 (0.0)	0.0 (NA)	0.0 (NA)
REC, Day 1 Pre-dose, n=3,1,2,0,0,2	0.0 (0.0)	0.0 (NA)	0.0 (0.0)	0.0 (0.0)
REC, Day 2 , n=1,0,3,1,1,2	0.0 (NA)	0.0 (0.0)	0.0 (NA)	0.0 (NA)	0.0 (0.0)
REC, Day 4, n=3,0,1,2,0,0	0.0 (0.0)	0.0 (NA)	0.0 (0.0)
REC, Day 7, n=4,0,2,2,0,0	0.0 (0.0)	0.0 (0.0)	0.0 (0.0)
SEC, Day -1 Pre-dose, n=1,0,2,1,0,1	0.0 (NA)	4.0 (5.66)	8.0 (NA)	3.0 (NA)
SEC, Day 1 Pre-dose, n=3,1,2,0,0,2	1.0 (1.73)	0.0 (NA)	2.0 (2.83)	1.5 (0.71)
SEC, Day 2 , n=1,0,3,1,1,2	0.0 (NA)	0.0 (0.0)	0.0 (NA)	0.0 (NA)	0.0 (0.0)
SEC, Day 4, n=3,0,1,2,0,0	0.0 (0.0)	10.0 (NA)	1.0 (1.41)
SEC, Day 7, n=4,0,2,2,0,0	1.5 (3.00)	0.0 (0.0)	11.0 (12.73)
Urine Erythrocytes,Day -1 Pre-dose, n=1,0,2,1,0,1	5.0 (NA)	0.5 (0.71)	3.0 (NA)	1.0 (NA)
Urine Erythrocytes,Day 1 Pre-dose, n=3,1,2,0,0,2	2.3 (4.04)	0.0 (NA)	0.0 (0.0)	0.0 (0.0)
Urine Erythrocytes,Day 2 , n=1,0,3,1,1,2	1.0 (NA)	0.0 (0.0)	7.0 (NA)	0.0 (NA)	0.5 (0.71)
Urine Erythrocytes,Day 4, n=3,0,1,2,0,0	1.0 (1.00)	2.0 (NA)	0.0 (0.0)
Urine Erythrocytes,Day 7, n=4,0,2,2,0,0	0.5 (1.00)	0.0 (0.0)	0.0 (0.0)
Urine Leukocytes,Day -1 Pre-dose, n=1,0,2,1,0,1	1.0 (NA)	1.5 (2.12)	1.0 (NA)	4.0 (NA)
Urine Leukocytes,Day 1 Pre-dose, n=3,1,2,0,0,2	5.0 (8.66)	0.0 (NA)	0.5 (0.71)	3.0 (2.83)
Urine Leukocytes,Day 2 , n=1,0,3,1,1,2	0.0 (NA)	0.0 (0.0)	4.0 (NA)	0.0 (NA)	0.5 (0.71)
Urine Leukocytes,Day 4, n=3,0,1,2,0,0	1.0 (1.73)	3.0 (NA)	42.0 (59.40)
Urine Leukocytes,Day 7, n=4,0,2,2,0,0	0.3 (0.50)	0.0 (0.0)	40.5 (55.86)

9. Primary Outcome

Title	Ketones and Urine Glucose at Indicated Time Points
Description	Urinalysis included parameters like ketones and urine glucose. Data at indicated time points were reported.
Time Frame	Pre-dose Day -1 and Day 1, Day 2, Day 4 and Day 7

Outcome Measure Data

Analysis Population Description

All Subjects Population

Arm/Group Title	Part 1: Placebo	Part 1: GSK1795091 7 ng	Part 1: GSK1795091 21 ng	Part 1: GSK1795091 60 ng	Part 1: GSK1795091 Repeated 60 ng	Part 1: GSK1795091 100 ng
Arm/Group Description	Participants in Part 1 were randomized to receive IV matching Placebo of GSK1795091. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 7 ng. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 21 ng. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 60 ng. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV repeat dose of GSK1795091 60 ng as the study was restarted. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 100 ng. Participants were observed inpatient until discharge on Day 5.
Measure Participants	10	6	6	6	6	6
Ketones, Pre-dose Day -1	0.05 (0.158)	0.00 (0.000)	0.08 (0.204)	0.00 (0.000)	0.00 (0.000)	0.25 (0.612)
Ketones, Pre-dose Day 1	0.05 (0.158)	0.00 (0.000)	0.25 (0.612)	0.00 (0.000)	0.00 (0.000)	0.08 (0.204)
Ketones, Day 2	0.00 (0.000)	0.00 (0.000)	0.00 (0.00)	0.00 (0.000)	0.00 (0.000)	1.75 (2.525)
Ketones, Day 4	0.15 (0.242)	0.00 (0.000)	0.08 (0.204)	0.00 (0.000)	0.00 (0.000)	0.08 (0.204)
Ketones, Day 7	0.00 (0.000)	0.00 (0.000)	0.08 (0.204)	0.25 (0.612)	0.00 (0.000)	0.08 (0.204)
Urine glucose, Pre-dose Day -1	0.0 (0.00)	0.0 (0.00)	0.0 (0.00)	0.0 (0.00)	0.0 (0.00)	0.0 (0.00)
Urine glucose, Pre-dose Day 1	0.0 (0.00)	0.0 (0.00)	0.0 (0.00)	0.0 (0.00)	0.0 (0.00)	0.0 (0.00)
Urine glucose, Day 2	0.0 (0.00)	0.0 (0.00)	0.0 (0.00)	0.0 (0.00)	0.0 (0.00)	0.0 (0.00)
Urine glucose, Day 4	0.0 (0.00)	0.0 (0.00)	0.0 (0.00)	0.0 (0.00)	0.0 (0.00)	0.0 (0.00)
Urine glucose, Day 7	0.0 (0.00)	0.0 (0.00)	0.0 (0.00)	0.0 (0.00)	0.0 (0.00)	0.0 (0.00)

10. Primary Outcome

Title	Occult Blood at Indicated Time Points
Description	Urinalysis included parameter like Occult blood. Data at indicated time points were reported.
Time Frame	Pre-dose Day -1 and Day 1, Day 2, Day 4 and Day 7

Outcome Measure Data

Analysis Population Description

All Subjects Population

Arm/Group Title	Part 1: Placebo	Part 1: GSK1795091 7 ng	Part 1: GSK1795091 21 ng	Part 1: GSK1795091 60 ng	Part 1: GSK1795091 Repeated 60 ng	Part 1: GSK1795091 100 ng
Arm/Group Description	Participants in Part 1 were randomized to receive IV matching Placebo of GSK1795091. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 7 ng. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 21 ng. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 60 ng. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV repeat dose of GSK1795091 60 ng as the study was restarted. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 100 ng. Participants were observed inpatient until discharge on Day 5.
Measure Participants	10	6	6	6	6	6
Pre-dose Day -1	2.5 (7.91)	0.0 (0.00)	5.8 (10.21)	0.0 (0.00)	0.0 (0.00)	0.0 (0.00)
Pre-dose Day 1	4.5 (8.32)	1.7 (4.08)	3.3 (5.16)	0.0 (0.00)	0.0 (0.00)	1.7 (4.08)
Day 2	2.5 (7.91)	0.0 (0.00)	5.0 (5.48)	4.2 (10.21)	1.7 (4.08)	5.8 (10.21)
Day 4	4.5 (8.32)	0.0 (0.00)	0.0 (0.00)	4.2 (10.21)	0.0 (0.00)	0.0 (0.00)
Day 7	4.0 (5.16)	0.0 (0.00)	8.3 (12.91)	0.0 (0.00)	0.0 (0.00)	0.0 (0.00)

11. Primary Outcome

Title	Urine Protein at Indicated Time Points
Description	Urinalysis included parameter like Urine protein. Data at indicated time points were reported.
Time Frame	Pre-dose Day -1 and Day 1, Day 2, Day 4 and Day 7

Outcome Measure Data

Analysis Population Description

All Subjects Population

Arm/Group Title	Part 1: Placebo	Part 1: GSK1795091 7 ng	Part 1: GSK1795091 21 ng	Part 1: GSK1795091 60 ng	Part 1: GSK1795091 Repeated 60 ng	Part 1: GSK1795091 100 ng
Arm/Group Description	Participants in Part 1 were randomized to receive IV matching Placebo of GSK1795091. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 7 ng. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 21 ng. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 60 ng. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV repeat dose of GSK1795091 60 ng as the study was restarted. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 100 ng. Participants were observed inpatient until discharge on Day 5.
Measure Participants	10	6	6	6	6	6
Pre-dose Day -1	0.000 (0.0000)	0.000 (0.0000)	0.042 (0.1021)	0.000 (0.0000)	0.000 (0.0000)	0.000 (0.0000)
Pre-dose Day 1	0.000 (0.0000)	0.000 (0.0000)	0.000 (0.0000)	0.000 (0.0000)	0.000 (0.0000)	0.000 (0.0000)
Day 2	0.000 (0.0000)	0.000 (0.0000)	0.000 (0.0000)	0.000 (0.0000)	0.000 (0.0000)	0.000 (0.0000)
Day 4	0.025 (0.0791)	0.000 (0.0000)	0.042 (0.1021)	0.000 (0.0000)	0.000 (0.0000)	0.000 (0.0000)
Day 7	0.000 (0.0000)	0.000 (0.0000)	0.042 (0.1021)	0.042 (0.1021)	0.000 (0.0000)	0.000 (0.0000)

12. Primary Outcome

Title	Specific Gravity at Indicated Time Points
Description	Urinalysis included parameter like specific gravity. Urinary specific gravity is a measure of the concentration of solutes in the urine. It measures the ratio of urine density compared with water density and provides information on the kidney's ability to concentrate urine.
Time Frame	Pre-dose Day -1 and Day 1, Day 2, Day 4 and Day 7

Outcome Measure Data

Analysis Population Description

All Subjects Population

Arm/Group Title	Part 1: Placebo	Part 1: GSK1795091 7 ng	Part 1: GSK1795091 21 ng	Part 1: GSK1795091 60 ng	Part 1: GSK1795091 Repeated 60 ng	Part 1: GSK1795091 100 ng
Arm/Group Description	Participants in Part 1 were randomized to receive IV matching Placebo of GSK1795091. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 7 ng. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 21 ng. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 60 ng. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV repeat dose of GSK1795091 60 ng as the study was restarted. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 100 ng. Participants were observed inpatient until discharge on Day 5.
Measure Participants	10	6	6	6	6	6
Pre-dose Day -1	1.018 (0.0065)	1.008 (0.0053)	1.017 (0.0091)	1.015 (0.0019)	1.008 (0.0030)	1.019 (0.0047)
Pre-dose Day 1	1.014 (0.0072)	1.011 (0.0048)	1.015 (0.0083)	1.013 (0.0063)	1.008 (0.0031)	1.014 (0.0060)
Day 2	1.017 (0.0049)	1.013 (0.0055)	1.017 (0.0041)	1.016 (0.0044)	1.014 (0.0048)	1.017 (0.0072)
Day 4	1.019 (0.0069)	1.014 (0.0041)	1.018 (0.0072)	1.016 (0.0038)	1.014 (0.0061)	1.016 (0.0059)
Day 7	1.016 (0.0082)	1.006 (0.0025)	1.015 (0.0117)	1.015 (0.0090)	1.010 (0.0079)	1.013 (0.0058)

13. Primary Outcome

Title	Urine Potential of Hydrogen (pH) at Indicated Time Points
Description	Urinalysis parameters included urine pH. pH is calculated on a scale of 0 to 14, values on the scale refer to the degree of alkalinity or acidity. A pH of 7 is neutral. A pH less than 7 is acidic, and a pH greater than 7 is basic. Normal urine has a slightly acid pH (5.0 - 6.0).
Time Frame	Pre-dose Day -1 and Day 1, Day 2, Day 4 and Day 7

Outcome Measure Data

Analysis Population Description

All Subject Population

Arm/Group Title	Part 1: Placebo	Part 1: GSK1795091 7 ng	Part 1: GSK1795091 21 ng	Part 1: GSK1795091 60 ng	Part 1: GSK1795091 Repeated 60 ng	Part 1: GSK1795091 100 ng
Arm/Group Description	Participants in Part 1 were randomized to receive IV matching Placebo of GSK1795091. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 7 ng. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 21 ng. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 60 ng. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV repeat dose of GSK1795091 60 ng as the study was restarted. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 100 ng. Participants were observed inpatient until discharge on Day 5.
Measure Participants	10	6	6	6	6	6
Pre-dose Day -1	6.10 (0.843)	6.42 (0.801)	5.00 (0.000)	5.83 (0.931)	6.50 (0.775)	5.67 (0.753)
Pre-dose Day 1	6.05 (0.926)	5.83 (0.931)	5.75 (0.822)	5.50 (0.837)	6.25 (0.758)	5.33 (0.816)
Day 2	6.20 (0.753)	5.83 (0.983)	5.92 (0.801)	6.25 (0.689)	5.33 (0.516)	5.50 (0.837)
Day 4	5.95 (0.725)	5.67 (1.033)	5.50 (0.775)	5.92 (1.021)	6.08 (0.917)	5.67 (0.816)
Day 7	6.00 (0.882)	5.58 (0.917)	5.25 (0.612)	5.75 (0.880)	5.92 (0.801)	6.08 (0.917)

14. Primary Outcome

Title	Number of Participants With Abnormal Electrocardiograms (ECG) Findings Worst Case Post-Baseline
Description	Single measurements of 12-lead ECGs were obtained after 10 minutes of rest in a semi-supine position for the participant. Participants with abnormal ECG findings that are clinically not significant (NCS) and clinically significant (CS) data has been presented here. The data of worst case post-Baseline is presented here.
Time Frame	Up to Day 32

Outcome Measure Data

Analysis Population Description

All Subjects Population.

Arm/Group Title	Part 1: Placebo	Part 1: GSK1795091 7 ng	Part 1: GSK1795091 21 ng	Part 1: GSK1795091 60 ng	Part 1: GSK1795091 Repeated 60 ng	Part 1: GSK1795091 100 ng
Arm/Group Description	Participants in Part 1 were randomized to receive IV matching Placebo of GSK1795091. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 7 ng. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 21 ng. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 60 ng. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV repeat dose of GSK1795091 60 ng as the study was restarted. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 100 ng. Participants were observed inpatient until discharge on Day 5.
Measure Participants	10	6	6	6	6	6
NCS	3 30%	1 16.7%	1 16.7%	2 33.3%	1 16.7%	1 16.7%
CS	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%

15. Secondary Outcome

Title	Maximum Observed Drug Concentration (Cmax) of GSK1795091 for Part 1
Description	Blood samples were collected at indicated time points. The Pharmacokinetic (PK) parameters were calculated for each participant using a non-compartmental method. All participants for whom, at least, one valid and evaluable pharmacokinetic parameter (AUC or Cmax) was derived were included in PK Parameter Population. Only those participants with data available at the specified data points were analyzed.
Time Frame	Pre-dose, 5 minutes, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, and 144 hours post-dose

Outcome Measure Data

Analysis Population Description

PK Parameter Population. NA indicates data was not available for 7 ng Arm as all concentration outcomes at 7 ng were not quantifiable because all results were below the limit of quantification.

Arm/Group Title	Part 1: GSK1795091 7 ng	Part 1: GSK1795091 21 ng	Part 1: GSK1795091 60 ng	Part 1: GSK1795091 Repeated 60 ng	Part 1: GSK1795091 100 ng
Arm/Group Description	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 7 ng. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 21 ng. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 60 ng. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV repeat dose of GSK1795091 60 ng as the study was restarted. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 100 ng. Participants were observed inpatient until discharge on Day 5.
Measure Participants	6	6	6	6	5
Geometric Mean (Geometric Coefficient of Variation) [Picogram/milliliter (pg/mL)]	NA (NA)	3.78 (15.9)	10.1 (13.0)	9.45 (25.5)	23.7 (6.69)

16. Secondary Outcome

Title	Time of Occurrence of Cmax (Tmax) and Terminal Half Life (t1/2) of GSK1795091 for Part 1
Description	Blood samples were collected at indicated time points. The PK parameters were calculated for each participant using a non-compartmental method. Only those participants with data available at the specified data points were analyzed.
Time Frame	Pre-dose, 5 minutes, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, and 144 hours post-dose

Outcome Measure Data

Analysis Population Description

PK Parameter Population. NA indicates data was not available for 7 ng Arm as all concentration outcomes at 7 ng were not quantifiable because all results were below the limit of quantification.

Arm/Group Title	Part 1: GSK1795091 7 ng	Part 1: GSK1795091 21 ng	Part 1: GSK1795091 60 ng	Part 1: GSK1795091 Repeated 60 ng	Part 1: GSK1795091 100 ng
Arm/Group Description	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 7 ng. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 21 ng. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 60 ng. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV repeat dose of GSK1795091 60 ng as the study was restarted. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 100 ng. Participants were observed inpatient until discharge on Day 5.
Measure Participants	6	6	6	6	5
t1/2	NA (NA)	25.2 (9.51)	45.7 (12.5)	67.1 (33.9)	69.4 (9.24)
tmax	NA (NA)	0.0950 (0.0197)	0.0833 (0.00816)	0.103 (0.0755)	0.0880 (0.0110)

17. Secondary Outcome

Title	Partial Area Under the Concentration-time Curve to Time t (AUC[0-t]), Area Under the Concentration-time Curve (AUC) From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC[0-inf]) of GSK1795091 for Part 1
Description	Blood samples were collected at indicated time points. The PK parameters were calculated for each participant using a non-compartmental method. AUC (0-t) was used interchangeably with AUC to last time of quantifiable concentration (AUC[0-last]) .Only those participants with data available at the specified data points were analyzed.
Time Frame	Pre-dose, 5 minutes, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, and 144 hours post-dose

Outcome Measure Data

Analysis Population Description

PK Parameter Population. NA indicates data was not available as all concentration outcomes at 7ng were not quantifiable because all results were below the limit of quantification.

Arm/Group Title	Part 1: GSK1795091 7 ng	Part 1: GSK1795091 21 ng	Part 1: GSK1795091 60 ng	Part 1: GSK1795091 Repeated 60 ng	Part 1: GSK1795091 100 ng
Arm/Group Description	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 7 ng. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 21 ng. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 60 ng. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV repeat dose of GSK1795091 60 ng as the study was restarted. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 100 ng. Participants were observed inpatient until discharge on Day 5.
Measure Participants	6	6	6	6	5
AUC(0-t)	NA (NA)	21.1 (89.7)	233 (56.4)	264 (33.3)	1100 (12.2)
AUC(0-inf)	NA (NA)	104 (52.2)	417 (40.0)	532 (26.3)	1440 (15.9)

18. Secondary Outcome

Title	Clearance (CL) of GSK1795091 for Part 1
Description	Blood samples were collected at indicated time points. The PK parameters were calculated for each participant using a non-compartmental method. Only those participants with data available at the specified data points were analyzed.
Time Frame	Pre-dose, 5 minutes, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, and 144 hours post-dose

Outcome Measure Data

Analysis Population Description

PK Parameter Population. NA indicates data was not available as all concentration outcomes at 7ng were not quantifiable because all results were below the limit of quantification.

Arm/Group Title	Part 1: GSK1795091 7 ng	Part 1: GSK1795091 21 ng	Part 1: GSK1795091 60 ng	Part 1: GSK1795091 Repeated 60 ng	Part 1: GSK1795091 100 ng
Arm/Group Description	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 7 ng. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 21 ng. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 60 ng. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV repeat dose of GSK1795091 60 ng as the study was restarted. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 100 ng. Participants were observed inpatient until discharge on Day 5.
Measure Participants	6	6	6	6	5
Geometric Mean (Geometric Coefficient of Variation) [Liters per hour (L/h)]	NA (NA)	0.202 (52.2)	0.144 (40.0)	0.113 (26.3)	0.0693 (15.9)

19. Secondary Outcome

Title	Volume of Distribution of GSK1795091 for Part 1
Description	Blood samples were collected at indicated time points. The PK parameters were calculated for each participant using a non-compartmental method. Only those participants with data available at the specified data points were analyzed.
Time Frame	Pre-dose, 5 minutes, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, and 144 hours post-dose

Outcome Measure Data

Analysis Population Description

PK Parameter Population. NA indicates data was not available as all concentration outcomes at 7ng were not quantifiable because all results were below the limit of quantification.

Arm/Group Title	Part 1: GSK1795091 7 ng	Part 1: GSK1795091 21 ng	Part 1: GSK1795091 60 ng	Part 1: GSK1795091 Repeated 60 ng	Part 1: GSK1795091 100 ng
Arm/Group Description	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 7 ng. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 21 ng. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 60 ng. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV repeat dose of GSK1795091 60 ng as the study was restarted. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 100 ng. Participants were observed inpatient until discharge on Day 5.
Measure Participants	6	6	6	6	5
Geometric Mean (Geometric Coefficient of Variation) [Liters (L)]	NA (NA)	6.95 (10.1)	9.46 (24.2)	9.95 (25.7)	6.75 (10.7)

20. Secondary Outcome

Title	Percentage Fold Change of Concentration of Interleukin 6 (IL-6) From Baseline for Part 1
Description	Blood samples were collected at indicated time points for the assessment of IL-6. Baseline (Day 1) was taken as the mean of the planned pre-dose measurements. Change from Baseline was defined as difference between the post-Baseline visit value and the Baseline value. Percentage fold change equals to 100*change from Baseline divided by Baseline. All participants in the "All Subjects Population" for whom valid and evaluable pharmacodynamic parameters were derived are included in Pharmacodynamic (PD) Population. Data from multiplex immunoassay has been reported.
Time Frame	Baseline, 1, 2, 4, 8, 12, 16, 24, 48 and 144 hours

Outcome Measure Data

Analysis Population Description

PD Population.

Arm/Group Title	Part 1: Placebo	Part 1: GSK1795091 7 ng	Part 1: GSK1795091 21 ng	Part 1: GSK1795091 60 ng	Part 1: GSK1795091 Repeated 60 ng	Part 1: GSK1795091 100 ng
Arm/Group Description	Participants in Part 1 were randomized to receive IV matching Placebo of GSK1795091. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 7 ng. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 21 ng. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 60 ng. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV repeat dose of GSK1795091 60 ng as the study was restarted. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 100 ng. Participants were observed inpatient until discharge on Day 5.
Measure Participants	10	6	6	6	6	5
1 hour	40.17 (51.192)	30.81 (33.517)	193.49 (163.904)	332.92 (310.845)	588.11 (324.942)	956.69 (763.404)
2 hour	26.49 (39.212)	239.27 (301.767)	625.51 (547.296)	1801.82 (1788.852)	2171.25 (1363.074)	7305.11 (6138.721)
4 hour	169.63 (421.394)	255.33 (254.874)	513.81 (523.303)	803.37 (1020.453)	1244.12 (1759.562)	1170.88 (767.439)
8 hour	262.38 (339.956)	161.33 (187.908)	338.13 (317.030)	166.86 (176.423)	677.24 (903.777)	190.07 (181.963)
12 hour	267.01 (274.112)	832.13 (965.345)	938.35 (1585.370)	500.75 (827.894)	644.77 (311.661)	363.91 (610.090)
16 hour	284.52 (356.147)	607.83 (986.760)	249.04 (280.046)	467.74 (620.968)	326.81 (300.766)	210.55 (425.106)
24 hour	129.34 (110.041)	200.07 (261.810)	56.24 (157.132)	182.47 (248.911)	201.93 (375.976)	160.58 (383.092)
48 hour	-13.13 (46.097)	-33.21 (30.172)	-18.95 (45.030)	-21.89 (30.042)	-14.22 (42.014)	-26.67 (21.931)
144 hour	-12.48 (27.665)	-29.63 (38.535)	-19.58 (26.650)	-4.52 (41.111)	-10.87 (26.937)	-6.59 (39.036)

21. Secondary Outcome

Title	Percentage Fold Change of Concentration of Tumor Necrosis Factor (TNF)-Alpha From Baseline for Part 1
Description	Blood samples were collected at indicated time points for the assessment of TNF-alpha. Baseline (Day 1) was taken as the mean of the planned pre-dose measurements. Change from Baseline was defined as difference between the post-Baseline visit value and the Baseline value. Percentage fold change equals to 100*change from Baseline divided by Baseline. Data from multiplex immunoassay has been reported. Only those participants with data available at the specified data points were analyzed (represented by n=X in category titles).
Time Frame	Baseline, 1, 2, 4, 8, 12, 16, 24, 48 and 144 hours

Outcome Measure Data

Analysis Population Description

PD Population.

Arm/Group Title	Part 1: Placebo	Part 1: GSK1795091 7 ng	Part 1: GSK1795091 21 ng	Part 1: GSK1795091 60 ng	Part 1: GSK1795091 Repeated 60 ng	Part 1: GSK1795091 100 ng
Arm/Group Description	Participants in Part 1 were randomized to receive IV matching Placebo of GSK1795091. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 7 ng. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 21 ng. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 60 ng. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV repeat dose of GSK1795091 60 ng as the study was restarted. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 100 ng. Participants were observed inpatient until discharge on Day 5.
Measure Participants	10	6	6	6	6	5
1 hour, n=8, 3, 5, 5, 4, 5	3.61 (28.753)	12.51 (22.453)	112.63 (185.111)	130.88 (126.286)	771.06 (579.613)	1838.09 (2790.783)
2 hour, n=8, 3, 5, 5, 4, 5	-1.26 (11.879)	-6.42 (5.229)	209.17 (437.355)	51.85 (58.482)	379.87 (299.578)	661.61 (998.133)
4 hour, n=8, 3, 5, 5, 4, 5	-4.38 (12.448)	-5.82 (8.277)	164.74 (402.327)	12.90 (22.215)	66.55 (76.017)	18.87 (26.716)
8 hour, n=8, 3, 5, 5, 4, 5	1.72 (8.690)	-12.56 (13.872)	75.34 (202.570)	2.28 (4.332)	11.12 (32.576)	-7.87 (10.985)
12 hour, n=8, 3, 5, 5, 4, 5	4.38 (19.376)	-10.33 (26.632)	54.30 (170.246)	7.61 (10.968)	24.14 (35.746)	-4.21 (9.459)
16 hour, n=8, 3, 5, 5, 4, 5	-1.81 (17.321)	-11.77 (16.419)	17.36 (92.732)	-1.28 (9.826)	43.11 (90.323)	-11.41 (14.569)
24 hour, n=8, 3, 5, 5, 4, 5	3.30 (30.223)	-10.02 (21.221)	17.39 (75.367)	7.26 (13.568)	34.79 (37.921)	-6.04 (17.245)
48 hour, n=8, 3, 5, 5, 3, 5	-2.56 (16.028)	-7.18 (9.567)	-10.99 (37.153)	4.03 (23.030)	-2.31 (45.586)	-13.33 (14.853)
144 hour, n=8, 3, 5, 5, 4, 5	-7.34 (15.006)	-2.90 (20.283)	-14.85 (27.169)	-2.10 (37.702)	5.46 (31.910)	-5.16 (17.479)

22. Secondary Outcome

Title	Percentage Fold Change of Concentration of Interferon (IFN)-Gamma From Baseline for Part 1
Description	Blood samples were collected at indicated time points for the assessment of IFN-gamma. Baseline (Day 1) was taken as the mean of the planned pre-dose measurements. Change from Baseline was defined as difference between the post-Baseline visit value and the Baseline value. Percentage fold change equals to 100*change from Baseline divided by Baseline. Data from multiplex immunoassay has been reported. Only those participants with data available at the specified data points were analyzed (represented by n=X in category titles).
Time Frame	Baseline, 1, 2, 4, 8, 12, 16, 24, 48 and 144 hours

Outcome Measure Data

Analysis Population Description

PD Population

Arm/Group Title	Part 1: Placebo	Part 1: GSK1795091 7 ng	Part 1: GSK1795091 21 ng	Part 1: GSK1795091 60 ng	Part 1: GSK1795091 Repeated 60 ng	Part 1: GSK1795091 100 ng
Arm/Group Description	Participants in Part 1 were randomized to receive IV matching Placebo of GSK1795091. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 7 ng. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 21 ng. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 60 ng. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV repeat dose of GSK1795091 60 ng as the study was restarted. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 100 ng. Participants were observed inpatient until discharge on Day 5.
Measure Participants	10	6	6	6	6	5
1 hour, n=9, 5, 4, 6, 6, 5	-1.24 (7.942)	-6.31 (7.547)	-3.16 (6.918)	-1.52 (3.299)	-8.15 (9.430)	14.42 (17.175)
2 hour, n=10, 5, 4, 6, 6, 5	5.04 (13.885)	-7.35 (10.068)	-0.81 (4.453)	17.81 (56.864)	72.02 (125.017)	104.54 (208.806)
4 hour, n=10, 5, 4, 6, 6, 5	-2.39 (8.391)	2.33 (6.932)	49.66 (97.641)	119.86 (211.426)	247.58 (188.954)	229.73 (352.909)
8 hour, n=10, 5, 4, 6, 6, 5	0.05 (5.453)	-0.10 (5.957)	13.68 (39.549)	36.75 (48.057)	86.13 (63.258)	66.69 (94.960)
12 hour, n=10, 5, 4, 6, 6, 5	4.48 (14.140)	-7.01 (27.233)	-9.18 (10.540)	20.90 (32.530)	38.35 (48.687)	31.00 (37.179)
16 hour, n=10, 5, 4, 6, 6, 5	6.51 (24.803)	-6.27 (29.923)	-15.42 (22.050)	20.62 (29.976)	34.82 (46.979)	12.75 (19.418)
24 hour, n=10, 4, 4, 6, 6, 5	3.96 (17.217)	6.57 (16.853)	-19.32 (32.943)	2.48 (8.071)	-3.08 (14.045)	6.46 (8.403)
48 hour, n=10, 4, 4, 6, 6, 5	4.21 (22.768)	1.41 (6.871)	-19.82 (34.669)	-3.63 (13.448)	0.39 (20.837)	2.43 (5.216)
144 hour, n=10, 4, 3, 6, 6, 5	33.01 (107.893)	4.96 (8.947)	-2.15 (13.149)	-4.16 (14.851)	6.81 (21.544)	-1.26 (5.652)

23. Secondary Outcome

Title	Percentage Fold Change of Concentration of Inducible Protein (IP)-10 From Baseline for Part 1
Description	Blood samples were collected at indicated time points for the assessment of IP-10. Baseline (Day 1) was taken as the mean of the planned pre-dose measurements. Change from Baseline was defined as difference between the post-Baseline visit value and the Baseline value. Percentage fold change equals to 100*change from Baseline divided by Baseline.
Time Frame	Baseline, 1, 2, 4, 8, 12, 16, 24, 48 and 144 hours

Outcome Measure Data

Analysis Population Description

PD Population

Arm/Group Title	Part 1: Placebo	Part 1: GSK1795091 7 ng	Part 1: GSK1795091 21 ng	Part 1: GSK1795091 60 ng	Part 1: GSK1795091 Repeated 60 ng	Part 1: GSK1795091 100 ng
Arm/Group Description	Participants in Part 1 were randomized to receive IV matching Placebo of GSK1795091. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 7 ng. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 21 ng. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 60 ng. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV repeat dose of GSK1795091 60 ng as the study was restarted. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 100 ng. Participants were observed inpatient until discharge on Day 5.
Measure Participants	10	6	6	6	6	5
1 hour	-17.09 (11.676)	-22.96 (9.621)	-10.99 (11.237)	-21.97 (10.771)	-6.50 (12.551)	14.49 (35.063)
2 hour	-15.30 (9.675)	-8.75 (16.126)	39.93 (26.514)	54.49 (58.967)	112.79 (66.958)	312.12 (121.798)
4 hour	-14.34 (11.025)	25.43 (42.934)	351.07 (286.393)	1672.77 (1676.676)	2045.12 (1937.378)	6740.10 (1888.455)
8 hour	-11.97 (10.564)	4.07 (29.521)	119.48 (103.465)	338.47 (349.007)	538.99 (614.669)	2367.11 (1067.103)
12 hour	-22.97 (8.906)	-9.76 (17.265)	46.78 (40.980)	133.47 (128.186)	337.37 (416.181)	802.21 (272.436)
16 hour	-14.51 (14.185)	-6.75 (20.215)	52.55 (32.122)	99.47 (114.305)	238.17 (321.382)	394.46 (171.075)
24 hour	-2.89 (20.587)	25.65 (38.100)	46.42 (25.692)	67.34 (34.573)	137.55 (128.045)	186.87 (57.860)
48 hour	6.24 (28.068)	37.30 (78.673)	31.98 (40.635)	35.61 (26.802)	41.03 (42.609)	57.44 (28.805)
144 hour	5.97 (35.519)	20.56 (41.682)	16.66 (39.635)	15.62 (50.973)	24.18 (21.117)	29.64 (21.330)

24. Secondary Outcome

Title	Percentage Fold Change of Concentration of Monocyte Chemotactic Protein 1 (MCP-1) From Baseline for Part 1
Description	Blood samples were collected at indicated time points for the assessment of MCP-1. Baseline (Day 1) was taken as the mean of the planned pre-dose measurements. Change from Baseline was defined as difference between the post-Baseline visit value and the Baseline value. Percentage fold change equals to 100*change from Baseline divided by Baseline.
Time Frame	Baseline, 1, 2, 4, 8, 12, 16, 24, 48 and 144 hours

Outcome Measure Data

Analysis Population Description

PD Population

Arm/Group Title	Part 1: Placebo	Part 1: GSK1795091 7 ng	Part 1: GSK1795091 21 ng	Part 1: GSK1795091 60 ng	Part 1: GSK1795091 Repeated 60 ng	Part 1: GSK1795091 100 ng
Arm/Group Description	Participants in Part 1 were randomized to receive IV matching Placebo of GSK1795091. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 7 ng. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 21 ng. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 60 ng. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV repeat dose of GSK1795091 60 ng as the study was restarted. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 100 ng. Participants were observed inpatient until discharge on Day 5.
Measure Participants	10	6	6	6	6	5
1 hour	0.39 (9.459)	-1.15 (10.591)	4.50 (12.165)	18.59 (24.366)	21.31 (30.421)	119.24 (58.836)
2 hour	0.73 (9.124)	76.83 (60.093)	481.09 (255.487)	1097.31 (743.475)	2604.72 (1691.082)	5883.27 (2461.263)
4 hour	-3.44 (14.828)	64.60 (54.045)	315.88 (237.902)	907.01 (928.980)	1241.68 (1744.836)	5290.85 (2834.623)
8 hour	1.97 (14.914)	7.94 (17.127)	35.25 (25.294)	51.16 (29.055)	70.82 (58.048)	223.95 (113.142)
12 hour	6.99 (16.748)	16.17 (18.245)	29.60 (25.748)	32.76 (23.618)	56.45 (56.466)	111.19 (67.497)
16 hour	11.29 (17.046)	29.40 (25.521)	26.43 (9.956)	35.30 (25.461)	39.71 (40.794)	45.49 (18.571)
24 hour	-6.26 (9.139)	-1.42 (9.045)	4.06 (7.179)	-7.95 (11.240)	3.90 (14.549)	10.69 (16.458)
48 hour	-3.16 (12.267)	-1.40 (9.991)	-1.51 (9.848)	-8.02 (15.104)	-7.40 (10.834)	-3.58 (10.363)
144 hour	13.23 (20.203)	24.53 (11.806)	22.01 (11.379)	8.74 (24.846)	14.97 (16.939)	15.23 (12.460)

25. Secondary Outcome

Title	Percentage Fold Change of Colony Stimulating Factor 2 (GCSF) From Baseline for Part 1
Description	Blood samples were collected at indicated time points for the assessment of GCSF. Baseline was taken as the mean of the planned pre-dose measurements. Change from Baseline was defined as difference between the post-Baseline visit value and the Baseline value. Percentage fold change equals to 100*change from Baseline divided by Baseline.
Time Frame	Baseline, 1, 2, 4, 8, 12, 16, 24, 48 and 144 hours

Outcome Measure Data

Analysis Population Description

PD Population

Arm/Group Title	Part 1: Placebo	Part 1: GSK1795091 7 ng	Part 1: GSK1795091 21 ng	Part 1: GSK1795091 60 ng	Part 1: GSK1795091 Repeated 60 ng	Part 1: GSK1795091 100 ng
Arm/Group Description	Participants in Part 1 were randomized to receive IV matching Placebo of GSK1795091. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 7 ng. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 21 ng. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 60 ng. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV repeat dose of GSK1795091 60 ng as the study was restarted. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 100 ng. Participants were observed inpatient until discharge on Day 5.
Measure Participants	10	6	6	6	6	5
1 hour	-0.99 (5.692)	-4.68 (10.515)	2.58 (7.662)	2.91 (16.607)	5.83 (8.244)	25.99 (11.220)
2 hour	2.91 (6.204)	2.69 (12.149)	11.12 (11.405)	162.85 (247.315)	105.64 (96.885)	1365.60 (893.674)
4 hour	10.78 (18.117)	4.38 (9.022)	13.23 (15.291)	933.31 (1826.357)	390.62 (541.504)	3754.71 (2439.913)
8 hour	19.67 (23.987)	16.22 (12.747)	9.78 (24.467)	150.61 (232.289)	96.07 (123.200)	595.98 (316.686)
12 hour	16.42 (20.532)	13.85 (17.900)	8.85 (20.773)	71.44 (71.786)	59.51 (72.401)	265.40 (166.832)
16 hour	5.83 (13.164)	10.84 (18.000)	-2.49 (17.532)	30.82 (39.981)	22.29 (55.206)	162.78 (121.912)
24 hour	6.67 (9.270)	4.50 (13.016)	1.23 (10.457)	23.82 (29.497)	15.76 (36.063)	96.88 (87.031)
48 hour	6.29 (12.038)	2.52 (10.170)	-1.26 (10.068)	19.14 (17.687)	3.08 (25.153)	17.08 (32.119)
144 hour	4.74 (19.231)	-10.01 (13.393)	7.06 (23.343)	-4.23 (16.821)	-5.25 (21.081)	-4.94 (23.010)

26. Secondary Outcome

Title	Percentage Fold Change of Interleukin 1 Receptor Antagonist (IL-1Ra) From Baseline for Part 1
Description	Blood samples were collected at indicated time points for the assessment of IL-1Ra. Baseline was taken as the mean of the planned pre-dose measurements. Change from Baseline was defined as difference between the post-Baseline visit value and the Baseline value. Percentage fold change equals to 100*change from Baseline divided by Baseline.
Time Frame	Baseline, 1, 2, 4, 8, 12, 16, 24, 48 and 144 hours

Outcome Measure Data

Analysis Population Description

PD Population

Arm/Group Title	Part 1: Placebo	Part 1: GSK1795091 7 ng	Part 1: GSK1795091 21 ng	Part 1: GSK1795091 60 ng	Part 1: GSK1795091 Repeated 60 ng	Part 1: GSK1795091 100 ng
Arm/Group Description	Participants in Part 1 were randomized to receive IV matching Placebo of GSK1795091. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 7 ng. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 21 ng. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 60 ng. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV repeat dose of GSK1795091 60 ng as the study was restarted. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 100 ng. Participants were observed inpatient until discharge on Day 5.
Measure Participants	10	6	6	6	6	5
1 hour	4.06 (12.046)	-1.63 (15.193)	11.49 (8.978)	19.88 (23.137)	38.00 (20.565)	111.99 (25.295)
2 hour	5.26 (17.249)	26.95 (19.100)	149.20 (53.633)	607.17 (611.511)	803.47 (486.468)	7054.40 (1029.027)
4 hour	13.43 (24.391)	196.62 (186.603)	1716.81 (1046.690)	12062.23 (13307.136)	13359.29 (9271.512)	105032.57 (61423.988)
8 hour	20.78 (28.762)	103.59 (63.317)	818.24 (578.438)	3136.61 (3429.187)	2788.30 (2101.015)	16830.47 (7106.072)
12 hour	21.64 (23.580)	99.49 (75.059)	360.87 (233.664)	1207.18 (1324.133)	1422.66 (1254.465)	7055.35 (3496.863)
16 hour	29.17 (28.404)	61.72 (38.867)	217.81 (154.263)	524.89 (652.117)	723.30 (718.195)	2273.75 (783.885)
24 hour	35.02 (51.217)	19.31 (36.307)	75.80 (64.742)	124.90 (154.983)	195.35 (136.345)	400.73 (98.553)
48 hour	-11.07 (23.224)	-3.86 (13.848)	10.45 (25.851)	7.64 (28.049)	15.71 (18.469)	37.51 (17.058)
144 hour	-2.00 (35.912)	-0.95 (19.617)	-2.03 (19.870)	3.17 (33.828)	3.26 (14.855)	2.75 (13.556)

27. Secondary Outcome

Title	Percentage Fold Change of Interleukin 10 (IL-10) From Baseline for Part 1
Description	Blood samples were collected at indicated time points for the assessment of IL-10. Baseline was taken as the mean of the planned pre-dose measurements. Change from Baseline was defined as difference between the post-Baseline visit value and the Baseline value. Percentage fold change equals to 100*change from Baseline divided by Baseline.
Time Frame	Baseline, 1, 2, 4, 8, 12, 16, 24, 48 and 144 hours

Outcome Measure Data

Analysis Population Description

PD Population

Arm/Group Title	Part 1: Placebo	Part 1: GSK1795091 7 ng	Part 1: GSK1795091 21 ng	Part 1: GSK1795091 60 ng	Part 1: GSK1795091 Repeated 60 ng	Part 1: GSK1795091 100 ng
Arm/Group Description	Participants in Part 1 were randomized to receive IV matching Placebo of GSK1795091. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 7 ng. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 21 ng. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 60 ng. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV repeat dose of GSK1795091 60 ng as the study was restarted. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 100 ng. Participants were observed inpatient until discharge on Day 5.
Measure Participants	10	6	6	6	6	5
1 hour	4.18 (2.923)	36.13 (50.565)	131.03 (167.082)	170.79 (130.626)	320.02 (171.738)	590.82 (378.761)
2 hour	3.89 (5.943)	138.05 (233.654)	496.20 (746.150)	437.92 (436.690)	587.14 (327.563)	2985.38 (2768.658)
4 hour	7.66 (9.351)	35.74 (39.419)	72.32 (81.429)	75.74 (75.003)	104.81 (83.542)	166.23 (149.184)
8 hour	1.45 (9.681)	13.56 (22.309)	44.31 (54.738)	38.31 (30.005)	98.31 (80.140)	152.84 (125.207)
12 hour	-0.94 (11.658)	4.52 (18.393)	22.10 (30.976)	18.10 (20.319)	39.32 (35.208)	46.01 (29.984)
16 hour	8.81 (23.057)	13.70 (20.597)	23.52 (32.664)	25.13 (19.212)	48.07 (34.705)	36.84 (22.787)
24 hour	14.43 (24.246)	6.07 (9.298)	11.37 (17.257)	16.47 (10.573)	24.70 (25.961)	21.83 (17.997)
48 hour	13.20 (45.366)	4.98 (5.925)	-1.41 (11.832)	9.63 (5.995)	-0.10 (8.984)	2.73 (10.103)
144 hour	17.99 (38.910)	15.53 (13.540)	10.35 (12.876)	11.73 (4.742)	14.73 (19.170)	7.28 (10.035)

28. Secondary Outcome

Title	Change From Baseline in WBC Differential for Part 1
Description	WBC differential included Lymphocytes Count, Monocytes Count, Granulocytes Count including neutrophils and eosinophil. Baseline (Day 1) was taken as the mean of the planned pre-dose measurements. Change from Baseline was defined as difference between the post-Baseline visit value and the Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n=X in category titles).
Time Frame	Baseline, 4, 24 and 144 hours

Outcome Measure Data

Analysis Population Description

All Subjects Population

Arm/Group Title	Part 1: Placebo	Part 1: GSK1795091 7 ng	Part 1: GSK1795091 21 ng	Part 1: GSK1795091 60 ng	Part 1: GSK1795091 Repeated 60 ng	Part 1: GSK1795091 100 ng
Arm/Group Description	Participants in Part 1 were randomized to receive IV matching Placebo of GSK1795091. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 7 ng. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 21 ng. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 60 ng. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV repeat dose of GSK1795091 60 ng as the study was restarted. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 100 ng. Participants were observed inpatient until discharge on Day 5.
Measure Participants	10	6	6	6	6	6
Monocytes count, 4 hour, n=10, 6, 6, 5, 6, 6	0.012 (0.0543)	0.156 (0.1228)	0.253 (0.0759)	0.129 (0.2242)	0.169 (0.1512)	-0.061 (0.1629)
Monocytes count, 24 hour, n=10, 6, 6, 6, 4, 6	0.072 (0.1631)	-0.038 (0.1411)	0.018 (0.0807)	0.035 (0.1415)	0.004 (0.0800)	0.104 (0.3037)
Monocytes count, 144 hour, n=10, 6, 6, 6, 6, 6	0.002 (0.0959)	0.013 (0.1454)	-0.054 (0.0746)	0.040 (0.1065)	-0.012 (0.0861)	-0.038 (0.0321)
Granulocytes Count, 4 hour, n=10, 6, 6, 5, 6, 6	0.076 (0.2703)	1.548 (0.8217)	3.708 (0.8286)	3.747 (2.3033)	3.856 (0.8005)	4.018 (4.9360)
Granulocytes Count, 24 hour, n=10, 6, 6, 6, 4, 6	0.400 (0.5482)	0.062 (0.7474)	-0.691 (0.8687)	-0.122 (0.6265)	-0.176 (0.3004)	-0.940 (2.3939)
Granulocytes Count, 144 hour, n=10, 6, 6, 6, 6, 6	-0.067 (0.9350)	0.292 (0.6764)	-0.669 (1.1381)	0.245 (0.9796)	-0.073 (1.0629)	-0.974 (1.9877)
Lymphocytes count, 4 hour, n=10, 6, 6, 5, 6, 6	0.082 (0.2017)	-0.118 (0.3070)	-0.603 (0.2988)	-0.393 (0.7111)	-0.997 (0.4404)	-1.419 (1.3685)
Lymphocytes count, 24 hour, n=10, 6, 6, 6, 4, 6	0.135 (0.2034)	-0.045 (0.2957)	-0.051 (0.2327)	0.042 (0.5468)	-0.247 (0.2634)	-0.489 (0.7405)
Lymphocytes count, 144 hour, n=10, 6, 6, 6, 6, 6	-0.080 (0.3950)	-0.107 (0.1786)	-0.030 (0.2490)	0.060 (0.6556)	-0.175 (0.5181)	-0.266 (0.6911)

29. Secondary Outcome

Title	Change From Baseline in CRP for Part 1
Description	Blood samples were collected at indicated time points for the assessment of CRP. Baseline was taken as the mean of the planned pre-dose measurements. Change from Baseline was defined as difference between the post-Baseline visit value and the Baseline value.
Time Frame	Baseline, Days 2, 4 and 7

Outcome Measure Data

Analysis Population Description

All Subjects Population

Arm/Group Title	Part 1: Placebo	Part 1: GSK1795091 7 ng	Part 1: GSK1795091 21 ng	Part 1: GSK1795091 60 ng	Part 1: GSK1795091 Repeated 60 ng	Part 1: GSK1795091 100 ng
Arm/Group Description	Participants in Part 1 were randomized to receive IV matching Placebo of GSK1795091. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 7 ng. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 21 ng. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 60 ng. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV repeat dose of GSK1795091 60 ng as the study was restarted. Participants were observed inpatient until discharge on Day 5.	In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 100 ng. Participants were observed inpatient until discharge on Day 5.
Measure Participants	10	6	6	6	6	6
Day 2	-0.074 (0.1852)	0.448 (0.7342)	4.550 (3.8044)	10.413 (10.7622)	11.900 (6.1323)	19.442 (1.9676)
Day 4	-0.101 (0.3839)	0.098 (0.1480)	0.748 (0.5974)	2.430 (2.3835)	2.362 (1.4852)	3.760 (1.2465)
Day 7	0.468 (1.3130)	0.338 (0.3712)	0.128 (0.3022)	4.802 (9.2888)	1.305 (0.8481)	1.428 (1.0400)

30. Secondary Outcome

Title	Maximum Observed Drug Concentration (Cmax) of GSK1795091 for Part 2
Description	Cmax assessment was planned for Part 2 after IV dose administration to healthy participants 1 or 2 Weeks after the first dose. The data for Part 2 of the study was not collected as the study was discontinued by the Sponsor prior to its scheduled start due to participant in Part 1 experienced the late occurrence of Adverse events (AEs) of unknown etiology.
Time Frame	Pre-dose, 5 minutes, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, and 144 hours post-dose

Outcome Measure Data

Analysis Population Description

PK Parameter Population. Data was not collected for Part 2 as none of the participant was enrolled into Part 2 of the study.

Arm/Group Title	All Participants in Part 2
Arm/Group Description	In part 2, two doses GSK1795091 determined by results from Part 1 were planned in parallel group evaluation. Part 2 was discontinued by the Sponsor prior to its scheduled start and no participants were enrolled.
Measure Participants	0

31. Secondary Outcome

Title	Time of Occurrence of Cmax (Tmax) and Terminal Half Life (t1/2) of GSK1795091 for Part 2
Description	Tmax and t1/2 assessments were planned for Part 2 after IV dose administration to healthy participants 1 or 2 Weeks after the first dose. The data for Part 2 of the study was not collected as the study was discontinued by the Sponsor prior to its scheduled start due to participant in Part 1 experienced the late occurrence of AEs of unknown etiology.
Time Frame	Pre-dose, 5 minutes, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, and 144 hours post-dose

Outcome Measure Data

Analysis Population Description

PK Parameter Population. Data was not collected for Part 2 as none of the participant was enrolled into Part 2 of the study.

Arm/Group Title	All Participants in Part 2
Arm/Group Description	In part 2, two doses GSK1795091 determined by results from Part 1 were planned in parallel group evaluation. Part 2 was discontinued by the Sponsor prior to its scheduled start and no participants were enrolled.
Measure Participants	0

32. Secondary Outcome

Title	Partial Area Under the Concentration-time Curve to Time = t (AUC[0-t]), Area Under the Concentration-time Curve (AUC) From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC[0-inf]) of GSK1795091 for Part 2
Description	AUC (0-t) and AUC (0-inf) assessments were planned for Part 2 after IV dose administration to healthy participants 1 or 2 Weeks after the first dose. The data for Part 2 of the study was not collected as the study was discontinued by the Sponsor prior to its scheduled start due to participant in Part 1 experienced the late occurrence of AEs of unknown etiology.
Time Frame	Pre-dose, 5 minutes, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, and 144 hours post-dose

Outcome Measure Data

Analysis Population Description

PK Parameter Population. Data was not collected for Part 2 as none of the participant was enrolled into Part 2 of the study.

Arm/Group Title	All Participants in Part 2
Arm/Group Description	In part 2, two doses GSK1795091 determined by results from Part 1 were planned in parallel group evaluation. Part 2 was discontinued by the Sponsor prior to its scheduled start and no participants were enrolled.
Measure Participants	0

33. Secondary Outcome

Title	Area Under the Concentration-time Curve (AUC) Time Curve for a Dosing Interval (AUC[0-tau]), AUC (0-last) of GSK1795091 for Part 2
Description	AUC (0-tau) and AUC (0-last) assessments were planned for Part 2 after IV dose administration to healthy participants 1 or 2 Weeks after the first dose. The data for Part 2 of the study was not collected as the study was discontinued by the Sponsor prior to its scheduled start due to participant in Part 1 experienced the late occurrence of AEs of unknown etiology.
Time Frame	Pre-dose, 5 minutes, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, and 144 hours post-dose

Outcome Measure Data

Analysis Population Description

PK Parameter Population. Data was not collected for Part 2 as none of the participant was enrolled into Part 2 of the study.

Arm/Group Title	All Participants in Part 2
Arm/Group Description	In part 2, two doses GSK1795091 determined by results from Part 1 were planned in parallel group evaluation. Part 2 was discontinued by the Sponsor prior to its scheduled start and no participants were enrolled.
Measure Participants	0

34. Secondary Outcome

Title	Clearance (CL) of GSK1795091 for Part 2
Description	CL assessment was planned for Part 2 after IV dose administration to healthy participants 1 or 2 Weeks after the first dose. The data for Part 2 of the study was not collected as the study was discontinued by the Sponsor prior to its scheduled start due to participant in Part 1 experienced the late occurrence of AEs of unknown etiology.
Time Frame	Pre-dose, 5 minutes, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, and 144 hours post-dose

Outcome Measure Data

Analysis Population Description

PK Parameter Population. Data was not collected for Part 2 as none of the participant was enrolled into Part 2 of the study.

Arm/Group Title	All Participants in Part 2
Arm/Group Description	In part 2, two doses GSK1795091 determined by results from Part 1 were planned in parallel group evaluation. Part 2 was discontinued by the Sponsor prior to its scheduled start and no participants were enrolled.
Measure Participants	0

35. Secondary Outcome

Title	Volume of Distribution of GSK1795091 for Part 2
Description	Volume of distribution assessment was planned for Part 2 after IV dose administration to healthy participants 1 or 2 Weeks after the first dose. The data for Part 2 of the study was not collected as the study was discontinued by the Sponsor prior to its scheduled start due to participant in Part 1 experienced the late occurrence of AEs of unknown etiology.
Time Frame	Pre-dose, 5 minutes, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, and 144 hours post-dose

Outcome Measure Data

Analysis Population Description

PK Parameter Population. Data was not collected for Part 2 as none of the participant was enrolled into Part 2 of the study.

Arm/Group Title	All Participants in Part 2
Arm/Group Description	In part 2, two doses GSK1795091 determined by results from Part 1 were planned in parallel group evaluation. Part 2 was discontinued by the Sponsor prior to its scheduled start and no participants were enrolled.
Measure Participants	0

36. Secondary Outcome

Title	Accumulation Ratio of GSK1795091 for Part 2
Description	Accumulation ratio assessment was planned for Part 2 after IV dose administration to healthy participants 1 or 2 Weeks after the first dose. The data for Part 2 of the study was not collected as the study was discontinued by the Sponsor prior to its scheduled start due to participant in Part 1 experienced the late occurrence of AEs of unknown etiology.
Time Frame	Pre-dose, 5 minutes, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, and 144 hours post-dose

Outcome Measure Data

Analysis Population Description

PK Parameter Population. Data were not collected for part 2 as none of the participant was enrolled into Part 2 of the study.

Arm/Group Title	All Participants in Part 2
Arm/Group Description	In part 2, two doses GSK1795091 determined by results from Part 1 were planned in parallel group evaluation. Part 2 was discontinued by the Sponsor prior to its scheduled start and no participants were enrolled.
Measure Participants	0

37. Secondary Outcome

Title	Time Invariance of GSK1795091 for Part 2
Description	Time invariance assessment was planned for Part 2 after IV dose administration to healthy participants 1 or 2 Weeks after the first dose. The data for Part 2 of the study was not collected as the study was discontinued by the Sponsor prior to its scheduled start due to participant in Part 1 experienced the late occurrence of AEs of unknown etiology.
Time Frame	Pre-dose, 5 minutes, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, and 144 hours post-dose

Outcome Measure Data

Analysis Population Description

PK Parameter Population. Data was not collected for Part 2 as none of the participant was enrolled into Part 2 of the study.

Arm/Group Title	All Participants in Part 2
Arm/Group Description	In part 2, two doses GSK1795091 determined by results from Part 1 were planned in parallel group evaluation. Part 2 was discontinued by the Sponsor prior to its scheduled start and no participants were enrolled.
Measure Participants	0

38. Secondary Outcome

Title	Percentage Fold Change of Concentration of Interleukin 6 (IL-6) From Baseline for Part 2
Description	IL-6 assessment was planned for Part 2 after IV dose administration to healthy participants 1 or 2 Weeks after the first dose. The data for Part 2 of the study was not collected as the study was discontinued by the Sponsor prior to its scheduled start due to participant in Part 1 experienced the late occurrence of AEs of unknown etiology.
Time Frame	Baseline, 1, 2, 4, 8, 12, 16, 24, 48 and 144 hours

Outcome Measure Data

Analysis Population Description

PD Population. Data was not collected for Part 2 as none of the participant was enrolled into Part 2 of the study.

Arm/Group Title	All Participants in Part 2
Arm/Group Description	In part 2, two doses GSK1795091 determined by results from Part 1 were planned in parallel group evaluation. Part 2 was discontinued by the Sponsor prior to its scheduled start and no participants were enrolled.
Measure Participants	0

39. Secondary Outcome

Title	Percentage Fold Change of Concentration of TNF-alpha From Baseline for Part 2
Description	TNF-alpha assessment was planned for Part 2 after IV dose administration to healthy participants 1 or 2 Weeks after the first dose. The data for Part 2 of the study was not collected as the study was discontinued by the Sponsor prior to its scheduled start due to participant in Part 1 experienced the late occurrence of AEs of unknown etiology.
Time Frame	Baseline, 1, 2, 4, 8, 12, 16, 24, 48 and 144 hours

Outcome Measure Data

Analysis Population Description

PD Population. Data was not collected for Part 2 as none of the participant was enrolled into Part 2 of the study.

Arm/Group Title	All Participants in Part 2
Arm/Group Description	In part 2, two doses GSK1795091 determined by results from Part 1 were planned in parallel group evaluation. Part 2 was discontinued by the Sponsor prior to its scheduled start and no participants were enrolled.
Measure Participants	0

40. Secondary Outcome

Title	Percentage Fold Change of Concentration of IFN-gamma From Baseline for Part 2
Description	IFN-gamma assessment was planned for Part 2 after IV dose administration to healthy participants 1 or 2 Weeks after the first dose. The data for Part 2 of the study was not collected as the study was discontinued by the Sponsor prior to its scheduled start due to participant in Part 1 experienced the late occurrence of AEs of unknown etiology.
Time Frame	Baseline, 1, 2, 4, 8, 12, 16, 24, 48 and 144 hours

Outcome Measure Data

Analysis Population Description

PD Population. Data was not collected for Part 2 as none of the participant was enrolled into Part 2 of the study.

Arm/Group Title	All Participants in Part 2
Arm/Group Description	In part 2, two doses GSK1795091 determined by results from Part 1 were planned in parallel group evaluation. Part 2 was discontinued by the Sponsor prior to its scheduled start and no participants were enrolled.
Measure Participants	0

41. Secondary Outcome

Title	Percentage Fold Change of Concentration of IP-10 From Baseline for Part 2
Description	IP-10 assessment was planned for Part 2 after IV dose administration to healthy participants 1 or 2 Weeks after the first dose. The data for Part 2 of the study was not collected as the study was discontinued by the Sponsor prior to its scheduled start due to participant in Part 1 experienced the late occurrence of AEs of unknown etiology.
Time Frame	Baseline, 1, 2, 4, 8, 12, 16, 24, 48 and 144 hours

Outcome Measure Data

Analysis Population Description

PD Population. The data was not collected for Part 2 because no Par. were enrolled into this part of the study.

Arm/Group Title	All Participants in Part 2
Arm/Group Description	In part 2, two doses GSK1795091 determined by results from Part 1 were planned in parallel group evaluation. Part 2 was discontinued by the Sponsor prior to its scheduled start and no participants were enrolled.
Measure Participants	0

42. Secondary Outcome

Title	Percentage Fold Change of Concentration of MCP-1 From Baseline for Part 2
Description	MCP-1 assessment was planned for Part 2 after IV dose administration to healthy participants 1 or 2 Weeks after the first dose. The data for Part 2 of the study was not collected as the study was discontinued by the Sponsor prior to its scheduled start due to participant in Part 1 experienced the late occurrence of AEs of unknown etiology.
Time Frame	Baseline, 1, 2, 4, 8, 12, 16, 24, 48 and 144 hours

Outcome Measure Data

Analysis Population Description

PD Population. Data was not collected for Part 2 as none of the participant was enrolled into Part 2 of the study.

Arm/Group Title	All Participants in Part 2
Arm/Group Description	In part 2, two doses GSK1795091 determined by results from Part 1 were planned in parallel group evaluation. Part 2 was discontinued by the Sponsor prior to its scheduled start and no participants were enrolled.
Measure Participants	0

43. Secondary Outcome

Title	Percentage Fold Change of Concentration of GCSF From Baseline for Part 2
Description	GCSF assessment was planned for Part 2 after IV dose administration to healthy participants 1 or 2 Weeks after the first dose. The data for Part 2 of the study was not collected as the study was discontinued by the Sponsor prior to its scheduled start due to participant in Part 1 experienced the late occurrence of AEs of unknown etiology.
Time Frame	Baseline, 1, 2, 4, 8, 12, 16, 24, 48 and 144 hours

Outcome Measure Data

Analysis Population Description

PD Population. Data was not collected for Part 2 as none of the participant was enrolled into Part 2 of the study.

Arm/Group Title	All Participants in Part 2
Arm/Group Description	In part 2, two doses GSK1795091 determined by results from Part 1 were planned in parallel group evaluation. Part 2 was discontinued by the Sponsor prior to its scheduled start and no participants were enrolled.
Measure Participants	0

44. Secondary Outcome

Title	Percentage Fold Change of Concentration of IL-1Ra From Baseline for Part 2
Description	IL-1Ra assessment was planned for Part 2 after IV dose administration to healthy participants 1 or 2 Weeks after the first dose. The data for Part 2 of the study was not collected as the study was discontinued by the Sponsor prior to its scheduled start due to participant in Part 1 experienced the late occurrence of AEs of unknown etiology.
Time Frame	Baseline, 1, 2, 4, 8, 12, 16, 24, 48 and 144 hours

Outcome Measure Data

Analysis Population Description

PD Population. The data was not collected for Part 2 because no Par. were enrolled into this part of the study.

Arm/Group Title	All Participants in Part 2
Arm/Group Description	In part 2, two doses GSK1795091 determined by results from Part 1 were planned in parallel group evaluation. Part 2 was discontinued by the Sponsor prior to its scheduled start and no participants were enrolled.
Measure Participants	0

45. Secondary Outcome

Title	Percentage Fold Change of Concentration of IL-10 From Baseline for Part 2
Description	IL-10 assessment was planned for Part 2 after IV dose administration to healthy participants 1 or 2 Weeks after the first dose. The data for Part 2 of the study was not collected as the study was discontinued by the Sponsor prior to its scheduled start due to participant in Part 1 experienced the late occurrence of AEs of unknown etiology.
Time Frame	Baseline, 1, 2, 4, 8, 12, 16, 24, 48 and 144 hours

Outcome Measure Data

Analysis Population Description

PD Population. The data was not collected for Part 2 because no Par. were enrolled into this part of the study.

Arm/Group Title	All Participants in Part 2
Arm/Group Description	In part 2, two doses GSK1795091 determined by results from Part 1 were planned in parallel group evaluation. Part 2 was discontinued by the Sponsor prior to its scheduled start and no participants were enrolled.
Measure Participants	0

46. Secondary Outcome

Title	Change From Baseline in WBC Differential for Part 2
Description	WBC differential assessment was planned for Part 2 after IV dose administration to healthy participants 1 or 2 Weeks after the first dose. The data for Part 2 of the study was not collected as the study was discontinued by the Sponsor prior to its scheduled start due to participant in Part 1 experienced the late occurrence of AEs of unknown etiology.
Time Frame	Baseline, 2, 24 and 144 hours

Outcome Measure Data

Analysis Population Description

All Subjects Population. Data was not collected for Part 2 as none of the participant was enrolled into Part 2 of the study.

Arm/Group Title	All Participants in Part 2
Arm/Group Description	In part 2, two doses GSK1795091 determined by results from Part 1 were planned in parallel group evaluation. Part 2 was discontinued by the Sponsor prior to its scheduled start and no participants were enrolled.
Measure Participants	0

47. Secondary Outcome

Title	Number of Participants With Urinalysis Parameters Outside Reference Range for Part 2
Description	Urinalysis as part of safety assessment was planned for Part 2 after IV dose administration to healthy participants 1 or 2 Weeks after the first dose. The data for Part 2 of the study was not collected as the study was discontinued by the Sponsor prior to its scheduled start due to participant in Part 1 experienced the late occurrence of AEs of unknown etiology.
Time Frame	Up to Day 7

Outcome Measure Data

Analysis Population Description

All Subjects Population. Data was not collected for Part 2 as none of the participant was enrolled into Part 2 of the study.

Arm/Group Title	All Participants in Part 2
Arm/Group Description	In part 2, two doses GSK1795091 determined by results from Part 1 were planned in parallel group evaluation. Part 2 was discontinued by the Sponsor prior to its scheduled start and no participants were enrolled.
Measure Participants	0

48. Secondary Outcome

Title	Number of Participants With Hematology Parameters Outside Reference Range in Part 2
Description	Hematology as part of safety assessment was planned for Part 2 after IV dose administration to healthy participants 1 or 2 Weeks after the first dose. The data for Part 2 of the study was not collected as the study was discontinued by the Sponsor prior to its scheduled start due to participant in Part 1 experienced the late occurrence of AEs of unknown etiology.
Time Frame	Up to Day 7

Outcome Measure Data

Analysis Population Description

All Subjects Population. Data was not collected for Part 2 as none of the participant was enrolled into Part 2 of the study.

Arm/Group Title	All Participants in Part 2
Arm/Group Description	In part 2, two doses GSK1795091 determined by results from Part 1 were planned in parallel group evaluation. Part 2 was discontinued by the Sponsor prior to its scheduled start and no participants were enrolled.
Measure Participants	0

49. Secondary Outcome

Title	Number of Participants With Clinical Chemistry Parameters Outside Reference Range in Part 2
Description	Clinical chemistry as part of safety assessment was planned for Part 2 after IV dose administration to healthy participants 1 or 2 Weeks after the first dose. The data for Part 2 of the study was not collected as the study was discontinued by the Sponsor prior to its scheduled start due to participant in Part 1 experienced the late occurrence of AEs of unknown etiology.
Time Frame	Up to Day 7

Outcome Measure Data

Analysis Population Description

All Subjects Population. Data was not collected for Part 2 as none of the participant was enrolled into Part 2 of the study.

Arm/Group Title	All Participants in Part 2
Arm/Group Description	In part 2, two doses GSK1795091 determined by results from Part 1 were planned in parallel group evaluation. Part 2 was discontinued by the Sponsor prior to its scheduled start and no participants were enrolled.
Measure Participants	0

50. Secondary Outcome

Title	Change From Baseline in CRP for Part 2
Description	CRP assessment was planned for Part 2 after IV dose administration to healthy participants 1 or 2 Weeks after the first dose. The data for Part 2 of the study was not collected as the study was discontinued by the Sponsor prior to its scheduled start due to participant in Part 1 experienced the late occurrence of AEs of unknown etiology.
Time Frame	Baseline and Pre-dose, 1, 2, 4, 8, 12, 16, 24, and 48 hours post dose

Outcome Measure Data

Analysis Population Description

All Subjects Population. Data was not collected for Part 2 as none of the participant was enrolled into Part 2 of the study.

Arm/Group Title	All Participants in Part 2
Arm/Group Description	In part 2, two doses GSK1795091 determined by results from Part 1 were planned in parallel group evaluation. Part 2 was discontinued by the Sponsor prior to its scheduled start and no participants were enrolled.
Measure Participants	0

51. Secondary Outcome

Title	Change From Baseline in Body Temperature for Part 2
Description	Body temperature was planned to be measured in Part 2 after IV dose administration to healthy participants 1 or 2 Weeks after the first dose. The data for Part 2 of the study was not collected as the study was discontinued by the Sponsor prior to its scheduled start due to participant in Part 1 experienced the late occurrence of AEs of unknown etiology.
Time Frame	Baseline and up to Day 7

Outcome Measure Data

Analysis Population Description

All Subjects Population. Data was not collected for Part 2 as none of the participant was enrolled into Part 2 of the study.

Arm/Group Title	All Participants in Part 2
Arm/Group Description	In part 2, two doses GSK1795091 determined by results from Part 1 were planned in parallel group evaluation. Part 2 was discontinued by the Sponsor prior to its scheduled start and no participants were enrolled.
Measure Participants	0

52. Secondary Outcome

Title	Change From Baseline in SBP and DBP for Part 2
Description	SBP and DBP was planned to be measured in Part 2 after IV dose administration to healthy participants 1 or 2 Weeks after the first dose. The data for Part 2 of the study was not collected as the study was discontinued by the Sponsor prior to its scheduled start due to participant in Part 1 experienced the late occurrence of AEs of unknown etiology.
Time Frame	Baseline and up to Day 7

Outcome Measure Data

Analysis Population Description

All Subjects Population. Data was not collected for Part 2 as none of the participant was enrolled into Part 2 of the study.

Arm/Group Title	All Participants in Part 2
Arm/Group Description	In part 2, two doses GSK1795091 determined by results from Part 1 were planned in parallel group evaluation. Part 2 was discontinued by the Sponsor prior to its scheduled start and no participants were enrolled.
Measure Participants	0

53. Secondary Outcome

Title	Change From Baseline in Respiratory Rate for Part 2
Description	Respiratory rate was planned to be measured in Part 2 after IV dose administration to healthy participants 1 or 2 Weeks after the first dose. The data for Part 2 of the study was not collected as the study was discontinued by the Sponsor prior to its scheduled start due to participant in Part 1 experienced the late occurrence of AEs of unknown etiology.
Time Frame	Baseline and up to Day 7

Outcome Measure Data

Analysis Population Description

All Subjects Population. Data was not collected for Part 2 as none of the participant was enrolled into Part 2 of the study.

Arm/Group Title	All Participants in Part 2
Arm/Group Description	In part 2, two doses GSK1795091 determined by results from Part 1 were planned in parallel group evaluation. Part 2 was discontinued by the Sponsor prior to its scheduled start and no participants were enrolled.
Measure Participants	0

54. Secondary Outcome

Title	Change From Baseline in Pulse Rate for Part 2
Description	Pulse rate was planned to be measured in Part 2 after IV dose administration to healthy participants 1 or 2 Weeks after the first dose. Baseline (Day 1) was taken as the mean of the planned pre-dose measurements. Change from Baseline was defined as difference between the post-Baseline visit value and the Baseline value. The data for Part 2 of the study was not collected as the study was discontinued by the Sponsor prior to its scheduled start due to participant in Part 1 experienced the late occurrence of AEs of unknown etiology.
Time Frame	Baseline and up to Day 7

Outcome Measure Data

Analysis Population Description

All Subjects Population. Data was not collected for Part 2 as none of the participant was enrolled into Part 2 of the study.

Arm/Group Title	All Participants in Part 2
Arm/Group Description	In part 2, two doses GSK1795091 determined by results from Part 1 were planned in parallel group evaluation. Part 2 was discontinued by the Sponsor prior to its scheduled start and no participants were enrolled.
Measure Participants	0

Adverse Events

Time Frame	Up to 102 days
Adverse Event Reporting Description	Non-serious AEs and SAE for All Subjects Population in Part 1 was reported. Non-serious AEs and SAE data was not collected for Part 2 as none of the participants were enrolled into Part 2 of the study.
Arm/Group Title	Part 1: Placebo		Part 1: GSK1795091 7 ng		Part 1: GSK1795091 21 ng		Part 1: GSK1795091 60 ng		Part 1: GSK1795091 Repeated 60 ng		Part 1: GSK1795091 100 ng		All Participants in Part 2
Arm/Group Description	Participants in Part 1 were randomized to receive IV matching Placebo of GSK1795091. Participants were observed inpatient until discharge on Day 5.		In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 7 ng. Participants were observed inpatient until discharge on Day 5.		In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 21 ng. Participants were observed inpatient until discharge on Day 5.		In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 60 ng. Participants were observed inpatient until discharge on Day 5.		In Part one sequential group evaluation, participants were randomized to receive single IV repeat dose of GSK1795091 60 ng as the study was restarted. Participants were observed inpatient until discharge on Day 5.		In Part one sequential group evaluation, participants were randomized to receive single IV dose of GSK1795091 100 ng. Participants were observed inpatient until discharge on Day 5.		In part 2, two doses GSK1795091 determined by results from Part 1 were planned in parallel group evaluation. Part 2 was discontinued by the Sponsor prior to its scheduled start and no participants were enrolled.
All Cause Mortality
	Part 1: Placebo		Part 1: GSK1795091 7 ng		Part 1: GSK1795091 21 ng		Part 1: GSK1795091 60 ng		Part 1: GSK1795091 Repeated 60 ng		Part 1: GSK1795091 100 ng		All Participants in Part 2
	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	0/10 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/0 (NaN)
Serious Adverse Events
	Part 1: Placebo		Part 1: GSK1795091 7 ng		Part 1: GSK1795091 21 ng		Part 1: GSK1795091 60 ng		Part 1: GSK1795091 Repeated 60 ng		Part 1: GSK1795091 100 ng		All Participants in Part 2
	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	0/10 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/0 (NaN)
Other (Not Including Serious) Adverse Events
	Part 1: Placebo		Part 1: GSK1795091 7 ng		Part 1: GSK1795091 21 ng		Part 1: GSK1795091 60 ng		Part 1: GSK1795091 Repeated 60 ng		Part 1: GSK1795091 100 ng		All Participants in Part 2
	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	0/10 (0%)		2/6 (33.3%)		0/6 (0%)		5/6 (83.3%)		3/6 (50%)		5/6 (83.3%)		0/0 (NaN)
Gastrointestinal disorders
Abdominal pain	0/10 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0	0/6 (0%)	0	0/0 (NaN)	0
General disorders
Influenza like illness	0/10 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	4/6 (66.7%)	4	1/6 (16.7%)	1	5/6 (83.3%)	5	0/0 (NaN)	0
Infections and infestations
Viral upper respiratory tract infection	0/10 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	0/0 (NaN)	0
Investigations
Body temperature increased	0/10 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	4/6 (66.7%)	6	0/6 (0%)	0	0/6 (0%)	0	0/0 (NaN)	0
Heart rate increased	0/10 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	4	0/6 (0%)	0	0/6 (0%)	0	0/0 (NaN)	0
Musculoskeletal and connective tissue disorders
Back pain	0/10 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	2/6 (33.3%)	2	0/0 (NaN)	0
Nervous system disorders
Headache	0/10 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	1/6 (16.7%)	1	1/6 (16.7%)	1	0/0 (NaN)	0
Dizziness	0/10 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	0/0 (NaN)	0
Presyncope	0/10 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	2/6 (33.3%)	2	0/0 (NaN)	0
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain	0/10 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	1/6 (16.7%)	1	0/6 (0%)	0	0/0 (NaN)	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.