Study of Danirixin in Japanese Healthy Elderly Male Subjects

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03136380
• Collaborator: (none)
• Enrollment: 34
• Locations: 2
• Arms: 5
• Actual Duration (Months): 2.7
• Patients Per Site: 17
• Patients Per Site Per Month: 6.3

Study Details

Study Description

Brief Summary

Danirixin is a selective chemokine receptor antagonist being developed as a potential anti-inflammatory agent for the treatment of chronic obstructive pulmonary disease (COPD). The aim of the study is to assess the safety, tolerability and pharmacokinetics (PK) in healthy Japanese subjects over the age of 65 years (inclusive). The study will be conducted in two parts: Part 1 will be a double blind, placebo-controlled, 3-period crossover, ascending single oral dose administration of GSK1325756H (Hydrobromide Salt Tablet Formulations of Danirixin) 10, 50 and 100 milligram (mg) in the fed condition. Part 2 will be an open label, 2-period crossover, single oral dose of GSK1325756H 50 mg in fed and fasted state. This study will provide an understanding of PK of hydrobromide salt of GSK1325756 in population of healthy elderly subjects and also contribute to the selection of appropriate dosing for Phase IIa study in Japan.

Condition or Disease	Intervention/Treatment	Phase
Pulmonary Disease, Chronic Obstructive	Drug: GSK1325756H; Drug: Placebo	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 34 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Single Centre, Double Blind (Sponsor Open), Placebo Controlled, 3-Period Crossover, Ascending Dose Study in Japanese Healthy Elderly Male Subjects to Evaluate the Safety, Tolerability and Pharmacokinetics of Danirixin in the Fed State (Part1) and an Open Label, 2-way Crossover to Evaluate Food Effect on the Pharmacokinetics of Danirixin (Part2)
• Actual Study Start Date: May 10, 2017
• Actual Primary Completion Date: Jul 31, 2017
• Actual Study Completion Date: Jul 31, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Part 1: Group A Subjects will receive GSK1325756H 10 mg in P-1, GSK1325756H 50 mg in P-2 and placebo in P-3 after a high fat meal. There will be a washout period of at least 7 days between each treatment period.	Drug: GSK1325756H; Danirixin will be available as 10 and 50 milligram (mg) white film coated, round and oval tablets intended for oral administration. It will be administered with 240 mL of water.; Drug: Placebo; Subjects will receive visually matching danirixin placebo tablets. It will be administered with 240 mL of water.
Experimental: Part 1: Group B Subjects will receive GSK1325756H 10 mg in P-1, placebo in P-2 and GSK1325756H 100 mg in P-3 after a high fat meal. There will be a washout period of at least 7 days between each treatment period.	Drug: GSK1325756H; Danirixin will be available as 10 and 50 milligram (mg) white film coated, round and oval tablets intended for oral administration. It will be administered with 240 mL of water.; Drug: Placebo; Subjects will receive visually matching danirixin placebo tablets. It will be administered with 240 mL of water.
Experimental: Part 1: Group C Subjects will receive placebo in P-1, GSK1325756H 50 mg in P-2 and GSK1325756H 100 mg in P-3 after a high fat meal. There will be a washout period of at least 7 days between each treatment period.	Drug: GSK1325756H; Danirixin will be available as 10 and 50 milligram (mg) white film coated, round and oval tablets intended for oral administration. It will be administered with 240 mL of water.; Drug: Placebo; Subjects will receive visually matching danirixin placebo tablets. It will be administered with 240 mL of water.
Experimental: Part 2: Group D Subjects will receive GSK1325756H 50 mg after a low fat meal and fasted state respectively. There will be a washout period of at least 7 days between each treatment period.	Drug: GSK1325756H; Danirixin will be available as 10 and 50 milligram (mg) white film coated, round and oval tablets intended for oral administration. It will be administered with 240 mL of water.
Experimental: Part 2: Group E Subjects will receive GSK1325756H 50 mg after a fasted state and a low fat meal respectively. There will be a washout period of at least 7 days between each treatment period.	Drug: GSK1325756H; Danirixin will be available as 10 and 50 milligram (mg) white film coated, round and oval tablets intended for oral administration. It will be administered with 240 mL of water.

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Any Adverse Event (AE) and Serious Adverse Events in Part 1 [Up to 32 days in Part 1]

   AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect or is medically significant. Safety population comprised of all participants who took at least one dose of study treatment.

2. Number of Participants With Any Adverse Event (AE) and Serious Adverse Events in Part 2 [Up to 21 days in Part 2]

   AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect or is medically significant

3. Change From Baseline in Clinical Laboratory Parameters Calcium, Cholesterol, Chloride, Glucose, High Density Lipids (HDL) Cholesterol, Potassium, Low Density Lipids (LDL) Cholesterol,Sodium,Phosphorus,Triglycerides,Urea/Blood Urea Nitrogen (BUN) in Part 1 [Baseline and up to 72 hours in Part 1]

   Blood samples were collected for the assessment of chemistry parameters namely calcium, cholesterol, chloride, glucose, HDL cholesterol, potassium, LDL cholesterol, sodium, phosphorus, triglycerides, and urea/BUN results for Part 1. Baseline was defined as assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose-visit value from the Baseline value. Only those participants with data available at the specified time were analyzed (represented by n=x in the category titles).

4. Change From Baseline in Clinical Chemistry Parameters Alkaline Phosphatase, Alanine Amino Transferase (ALT), Aspartate Amino Transferase (AST), Creatine Kinase, Gamma Glutamyl Transferase (GGT) and Lactate Dehydrogenase for Part 1 [Baseline and up to 72 hours in Part 1]

   Blood samples were collected for the assessment of chemistry parameters namely alkaline phosphatase, ALT, AST, creatine kinase, GGT and lactate dehydrogenase for Part 1. Baseline was defined as assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose-visit value from the Baseline value. Only those participants with data available at the specified time were analyzed (represented by n=x in the category titles).

5. Change From Baseline in Clinical Chemistry Parameters Albumin and Total Protein for Part 1 [Baseline and up to 72 hours in Part 1]

   Blood samples were collected for the assessment of chemistry parameters namely albumin and total protein for Part 1. Baseline was defined as assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose-visit value from the Baseline value. Only those participants with data available at the specified time were analyzed (represented by n=x in the category titles).

6. Change From Baseline in Clinical Chemistry Parameters Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid for Part 1 [Baseline and up to 72 hours in Part 1]

   Blood samples were collected for the assessment of chemistry parameters namely direct bilirubin, total bilirubin, creatinine and uric acid for Part 1. Baseline was defined as assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose-visit value from the Baseline value. Only those participants with data available at the specified time were analyzed (represented by n=x in the category titles).

7. Change From Baseline in Clinical Chemistry Parameter Amylase for Part 1 [Baseline and up to 72 hours in Part 1]

   Blood samples were collected for the assessment of chemistry parameters namely amylase for Part 1. Baseline was defined as assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose-visit value from the Baseline value. Only those participants with data available at the specified time were analyzed (represented by n=x in the category titles).

8. Change From Baseline in Clinical Laboratory Parameters Calcium, Cholesterol, Chloride, Glucose, HDL Cholesterol, Potassium, LDL Cholesterol, Sodium, Phosphorus Inorganic, Triglycerides, Urea/BUN for Part 2 [Baseline and up to 48 hours in Part 2]

   Blood samples were collected for the assessment of chemistry parameters namely calcium, cholesterol, chloride, glucose, HDL cholesterol, potassium, LDL cholesterol, sodium, phosphorus, triglycerides, urea/BUN results for Part 2. Baseline was defined as assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose-visit value from the Baseline value.

9. Change From Baseline in Clinical Chemistry Parameters Alkaline Phosphatase, ALT, AST, Creatine Kinase, GGT and Lactate Dehydrogenase for Part 2 [Baseline and up to 48 hours in Part 2]

   Blood samples were collected for the assessment of chemistry parameters namely alkaline phosphatase, ALT, AST, creatine kinase, GGT and lactate dehydrogenase for Part 2. Baseline was defined as assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose-visit value from the Baseline value.

10. Change From Baseline in Clinical Chemistry Parameters Albumin and Total Protein for Part 2 [Baseline and up to 48 hours in Part 2]

    Blood samples were collected for the assessment of chemistry parameters namely albumin and total protein for Part 2. Baseline was defined as assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose-visit value from the Baseline value.

11. Change From Baseline in Clinical Chemistry Parameters Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid for Part 2 [Baseline and up to 48 hours in Part 2]

    Blood samples were collected for the assessment of chemistry parameters namely direct bilirubin, total bilirubin, creatinine and uric acid for Part 2. Baseline was defined as assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose-visit value from the Baseline value.

12. Change From Baseline in Clinical Chemistry Parameter Amylase for Part 2 [Baseline and up to 48 hours in Part 2]

    Blood samples were collected for the assessment of chemistry parameter namely amylase for Part 1. Baseline was defined as assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose-visit value from the Baseline value.

13. Change From Baseline in Hematology Parameters Basophils, Eosinophils, Lymphocytes, Monocytes and Total Neutrophils for Part 1 [Baseline and up to 72 hours in Part 1]

    Blood samples were collected for the assessment of hematology parameters namely basophils, eosinophils, leukocytes, lymphocytes, monocytes, total neutrophils and platelets for Part 1. Baseline was defined as assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose-visit value from the Baseline value. Only those participants with data available at the specified time were analyzed (represented by n=x in the category titles).

14. Change From Baseline in Hematology Parameter Hemoglobin for Part 1 [Baseline and up to 72 hours in Part 1]

    Blood samples were collected for the assessment of hematology parameter namely hemoglobin for Part 1. Baseline was defined as assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose-visit value from the Baseline value. Only those participants with data available at the specified time were analyzed (represented by n=x in the category titles).

15. Change From Baseline in Hematology Parameter Hematocrit for Part 1 [Baseline and up to 72 hours in Part 1]

    Blood samples were collected for the assessment of hematology parameter namely hematocrit for Part 1. Baseline was defined as assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose-visit value from the Baseline value. Only those participants with data available at the specified time were analyzed (represented by n=x in the category titles).

16. Change From Baseline in Hematology Parameter Mean Corpuscle Hemoglobin for Part 1 [Baseline and up to 72 hours in Part 1]

    Blood samples were collected for the assessment of hematology parameter namely mean corpuscle hemoglobin for Part 1. Baseline was defined as assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose-visit value from the Baseline value. Only those participants with data available at the specified time were analyzed (represented by n=x in the category titles).

17. Change From Baseline in Hematology Parameter Mean Corpuscle Volume for Part 1 [Baseline and up to 72 hours in Part 1]

    Blood samples were collected for the assessment of hematology parameter namely mean corpuscle volume for Part 1. Baseline was defined as assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose-visit value from the Baseline value. Only those participants with data available at the specified time were analyzed (represented by n=x in the category titles).

18. Change From Baseline in Hematology Parameters Platelet Count and White Blood Cell Count for Part 1 [Baseline and up to 72 hours in Part 1]

    Blood samples were collected for the assessment of hematology parameters namely platelet count and white blood cell count for Part 1. Baseline was defined as assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose-visit value from the Baseline value. Only those participants with data available at the specified time were analyzed (represented by n=x in the category titles).

19. Change From Baseline in Hematology Parameters Red Blood Count and Reticulocyte Count for Part 1 [Baseline and up to 72 hours in Part 1]

    Blood samples were collected for the assessment of hematology parameters namely red blood count and reticulocyte count for Part 1. Baseline was defined as assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose-visit value from the Baseline value. Only those participants with data available at the specified time were analyzed (represented by n=x in the category titles).

20. Change From Baseline in Hematology Parameters Basophils, Eosinophils, Lymphocytes, Monocytes and Total Neutrophils for Part 2 [Baseline and up to 48 hours in Part 2]

    Blood samples were collected for the assessment of hematology parameters namely basophils, eosinophils, leukocytes, lymphocytes, monocytes, total neutrophils and platelets for Part 2. Baseline was defined as assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose-visit value from the Baseline value.

21. Change From Baseline in Hematology Parameter Hemoglobin for Part 2 [Baseline and up to 48 hours in Part 2]

    Blood samples were collected for the assessment of hematology parameter namely hemoglobin for Part 2. Baseline was defined as assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose-visit value from the Baseline value.

22. Change From Baseline in Hematology Parameter Hematocrit for Part 2 [Baseline and up to 48 hours in Part 2]

    Blood samples were collected for the assessment of hematology parameter namely hematocrit for Part 2. Baseline was defined as assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose-visit value from the Baseline value.

23. Change From Baseline in Hematology Parameter Mean Corpuscle Hemoglobin for Part 2 [Baseline and up to 48 hours in Part 2]

    Blood samples were collected for the assessment of hematology parameter namely mean corpuscle hemoglobin for Part 2. Baseline was defined as assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose-visit value from the Baseline value.

24. Change From Baseline in Hematology Parameter Mean Corpuscle Volume for Part 2 [Baseline and up to 48 hours in Part 2]

    Blood samples were collected for the assessment of hematology parameter namely mean corpuscle volume for Part 2. Baseline was defined as assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose-visit value from the Baseline value.

25. Change From Baseline in Hematology Parameters Platelet Count and White Blood Cell Count for Part 2 [Baseline and up to 48 hours in Part 2]

    Blood samples were collected for the assessment of hematology parameters namely platelet count and white blood cell count for Part 2. Baseline was defined as assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose-visit value from the Baseline value.

26. Change From Baseline in Hematology Parameters Red Blood Count and Reticulocyte Count for Part 2 [Baseline and up to 48 hours in Part 2]

    Blood samples were collected for the assessment of hematology parameters namely red blood count and reticulocyte count for Part 2. Baseline was defined as assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose-visit value from the Baseline value.

27. Number of Participants With Abnormal Values on Urinalysis by Dipstick Method for Part 1 [Up to 72 hours in Part 1]

    Urinalysis parameters assessed were urine bilirubin, urine occult blood, urine glucose, urine ketones, urine protein and urine urobilinogen. In this dipstick test, the level of bilirubin, occult blood, glucose, ketones, urine protein and urobilinogen in urine samples was recorded as negative, trace and +. Urine samples were collected for the measurement of urinalysis parameters by dipstick method up to 72 hours in Part 1. Only categories with significant values have been presented.

28. Urine Potential of Hydrogen (pH) Analysis by Dipstick Method for Part 1 [Up to 72 hours in Part 1]

    Urinary pH measurement is a routine part of urinalysis. Urine pH is an acid-base measurement. pH is measured on a numeric scale ranging from 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). Urine samples were collected for the measurement of urine pH by method up to 72 hours in Part 1. Only those participants with data available at the specified time were analyzed (represented by n=x in the category titles).

29. Urine Specific Gravity Analysis by Dipstick Method for Part 1 [Up to 72 hours in Part 1]

    Urinary specific gravity measurement is a routine part of urinalysis. Urine specific gravity is a measure of the concentration of solutes in the urine and provides information on the kidney's ability to concentrate urine. The concentration of the excreted molecules determines the urine's specific gravity. Urine samples were collected for the measurement of urine specific gravity by dipstick method up to 72 hours in Part 1. Only those participants with data available at the specified time were analyzed (represented by n=x in the category titles). Density is the mass per unit volume and has units (such as g/cm^3), however, the specific gravity is a ratio so it has no unit.

30. Number of Participants With Abnormal Values on Urinalysis by Dipstick Method for Part 2 [Up to 48 hours in Part 2]

    Urinalysis parameters assessed were urine bilirubin, urine occult blood, urine glucose, urine ketones, urine protein and urine urobilinogen. In this dipstick test, the level of bilirubin, occult blood, glucose, ketones, urine protein and urobilinogen in urine samples was recorded as negative, trace and +. Urine samples were collected for the measurement of urinalysis parameters by dipstick method up to 48 hours in Part 2. Only categories with significant values have been presented.

31. Urine pH Analysis by Dipstick Method for Part 2 [Up to 48 hours in Part 2]

    Urinary pH measurement is a routine part of urinalysis. Urine pH is an acid-base measurement. pH is measured on a numeric scale ranging from 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). Urine samples were collected for the measurement of urine pH by dipstick method up to 48 hours in Part 2.

32. Urine Specific Gravity Analysis by Dipstick Method for Part 2 [Up to 72 hours in Part 2]

    Urinary specific gravity measurement is a routine part of urinalysis. Urine specific gravity is a measure of the concentration of solutes in the urine and provides information on the kidney's ability to concentrate urine. The concentration of the excreted molecules determines the urine's specific gravity. Urine samples were collected for the measurement of urine specific gravity by dipstick method up to 48 hours in Part 2. Density is the mass per unit volume and has units (such as g/cm^3), however, the specific gravity is a ratio so it has no unit.

33. Change From Baseline in Vital Sign Parameters Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) for Part 1 [Baseline and up to 72 hours in Part 1]

    Vital sign measurements included SBP and DBP at Baseline and up to 72 hours in Part 1. SBP and DBP measurements were preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions and were measured in a supine position after 5 minutes rest. Baseline was defined as pre-dose assessments performed on Day 1. Change from Baseline was calculated by subtracting the post-dose-visit value from the Baseline value. Only those participants with data available at the specified time were analyzed (represented by n=x in the category titles).

34. Change From Baseline in Vital Sign Parameter Heart Rate for Part 1 [Baseline and up to 72 hours in Part 1]

    Vital sign measurements included heart rate at Baseline and up to 72 hours in Part 1. Heart rate measurements were preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions and were measured in a supine position after 5 minutes rest. Baseline was defined as pre-dose assessments performed on Day 1. Change from Baseline was calculated by subtracting the post-dose-visit value from the Baseline value. Only those participants with data available at the specified time were analyzed (represented by n=x in the category titles).

35. Change From Baseline in Vital Sign Parameter Temperature for Part 1 [Baseline and up to 72 hours in Part 1]

    Vital sign measurements included temperature at Baseline and up to 72 hours in Part 1. Temperature measurements were preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions and were measured in a supine position after 5 minutes rest. Baseline was defined as pre-dose assessments performed on Day 1. Change from Baseline was calculated by subtracting the post-dose-visit value from the Baseline value. Only those participants with data available at the specified time were analyzed (represented by n=x in the category titles).

36. Change From Baseline in Vital Sign Parameters SBP and DBP for Part 2 [Baseline and up to 48 hours in Part 2]

    Vital sign measurements included SBP and DBP at Baseline and up to 72 hours in Part 2. SBP and DBP measurements were preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions and were measured in a supine position after 5 minutes rest. Baseline was defined as pre-dose assessments performed on Day 1. Change from Baseline was calculated by subtracting the post-dose-visit value from the Baseline value.

37. Change From Baseline in Vital Sign Parameter Heart Rate for Part 2 [Baseline and up to 48 hours in Part 2]

    Vital sign measurements included heart rate at Baseline and up to 72 hours in Part 2. Heart rate measurements were preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions and were measured in a supine position after 5 minutes rest. Baseline was defined as pre-dose assessments performed on Day 1. Change from Baseline was calculated by subtracting the post-dose-visit value from the Baseline value.

38. Change From Baseline in Vital Sign Parameter Temperature for Part 2 [Baseline and up to 48 hours in Part 2]

    Vital sign measurements included temperature at Baseline and up to 72 hours in Part 2. Temperature measurements were preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions and were measured in a supine position after 5 minutes rest. Baseline was defined as pre-dose assessments performed on Day 1. Change from Baseline was calculated by subtracting the post-dose-visit value from the Baseline value.

39. Change From Baseline in Electrocardiogram (ECG) Parameters PR Interval, QRS Duration, Uncorrected QT Interval and Corrected QT Frederica's Correction) Interval [Baseline and up to 72 hours in Part 1]

    Single 12-lead ECG's were obtained from Baseline and up to 72 hours in Part 1 using an ECG machine that automatically calculated the heart rate and measured PR Interval, QRS Duration, Uncorrected QT interval and Corrected QT (Fridericia's correction) interval. Baseline was defined as pre-dose assessments performed on Day 1. Change from Baseline was calculated by subtracting the post-dose-visit value from the Baseline value. Only those participants with data available at the specified time were analyzed (represented by n=x in the category titles).

40. Change From Baseline in Electrocardiogram Parameters PR Interval, QRS Duration, Uncorrected QT Interval and Corrected QT (Frederica's Correction) Interval for Part 2 [Baseline and up to 48 hours in Part 2]

    Single 12-lead ECG's were obtained from Baseline and up to 72 hours in Part 2 using an ECG machine that automatically calculated the heart rate and measured PR Interval, QRS Duration, Uncorrected QT interval and Corrected QT (Frederica's correction) interval. Baseline was defined as pre-dose assessments performed on Day 1. Change from Baseline was calculated by subtracting the post-dose-visit value from the Baseline value.

41. Blood Concentration of GSK1325756 in Part 1 [Pre-dose and at 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours in all 3 periods; 60 and 72 hours post-dose in period-3 of Part 1]

    Whole blood samples of approximately 1 milliliters were collected for measurement of blood concentrations of GSK1325756 at pre-dose and at 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours in all 3 periods; 60 and 72 hours post-dose in period-3 of part 1. Data has been presented for blood concentrations of GSK1325756 in fed state. Pharmacokinetic (PK) population was defined as participants who were administered at least one dose of study treatment and who had PK sample taken and analyzed. NA indicates standard deviation could not be calculated due to high proportion of non-quantifiable [NQ] values (more than 30% of values were imputed i.e., NQ assigned zero concentration) which affected the standard deviation and no sample was obtained per protocol for 60 and 72 hours.

42. Blood Concentration of GSK1325756 in Part 2 [Pre-dose and at 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours post-dose in Part 2]

    Whole blood samples of approximately 1 milliliters were collected for measurement of blood concentrations of GSK1325756 at Pre-dose and at 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours post-dose in part 1. Data has been presented for blood concentrations of GSK1325756 in fasted and fed state. NA indicates standard deviation could not be calculated due to high proportion of NQ values (more than 30% of values were imputed i.e., NQ assigned zero concentration) which affected the standard deviation.

43. Maximum Observed Concentration (Cmax) of GSK1325756H for Part 1 [Pre-dose and at 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours in all 3 periods; 60 and 72 hours post-dose in period-3 of Part 1]

    Blood samples were collected at the indicated time points after administration of study treatment to investigate the PK profile of GSK1325756H in fasted state. PK parameters were calculated by standard non-compartmental analysis using Phoenix WinNonlin Version 6.4 or higher based on actual sampling times.

44. Area Under the Concentration-time Curve From Time 0 to t (AUC [0-t]) of GSK1325756H for Part 1 [Pre-dose and at 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours in all 3 periods; 60 and 72 hours post-dose in period-3 of Part 1]

    Blood samples were collected at the indicated time points after administration of study treatment to investigate the PK profile of GSK1325756H in fasted state. PK parameters were calculated by standard non-compartmental analysis using Phoenix WinNonlin Version 6.4 or higher based on actual sampling times.

45. Area Under the Concentration-time Curve From Time 0 to Infinity (AUC [0-inf]) of GSK1325756H for Part 1 [Pre-dose and at 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours in all 3 periods; 60 and 72 hours post-dose in period-3 of Part 1]

    Blood samples were collected at the indicated time points after administration of study treatment to investigate the PK profile of GSK1325756H in fasted state. PK parameters were calculated by standard non-compartmental analysis using Phoenix WinNonlin Version 6.4 or higher based on actual sampling times.

46. Area Under the Concentration-time Curve From Time 0 to 24 Hours (AUC [0-24]) of GSK1325756H for Part 1 [Pre-dose and at 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours in all 3 periods; 60 and 72 hours post-dose in period-3 of Part 1]

    Blood samples were collected at the indicated time points after administration of study treatment to investigate the PK profile of GSK1325756H in fasted state. PK parameters were calculated by standard non-compartmental analysis using Phoenix WinNonlin Version 6.4 or higher based on actual sampling times.

47. Time to Maximum Observed Concentration (Tmax) of GSK1325756H for Part 1 [Pre-dose and at 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours in all 3 periods; 60 and 72 hours post-dose in period-3 of Part 1]

    Blood samples were collected at the indicated time points after administration of study treatment to investigate the PK profile of GSK1325756H in fasted state. PK parameters were calculated by standard non-compartmental analysis using Phoenix WinNonlin Version 6.4 or higher based on actual sampling times.

48. Terminal Half-life (t1/2) of GSK1325756H for Part 1 [Pre-dose and at 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours in all 3 periods; 60 and 72 hours post-dose in period-3 of Part 1]

    Blood samples were collected at the indicated time points after administration of study treatment to investigate the PK profile of GSK1325756 in fasted state. PK parameters were calculated by standard non-compartmental analysis using Phoenix WinNonlin Version 6.4 or higher based on actual sampling times.

49. Lag Time Before Observable Concentration (Tlag) of GSK1325756H for Part 1 [Pre-dose and at 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours in all 3 periods; 60 and 72 hours post-dose in period-3 of Part 1]

    Blood samples were collected at the indicated time points after administration of study treatment to investigate the PK profile of GSK1325756 in fasted state. PK parameters were calculated by standard non-compartmental analysis using Phoenix WinNonlin Version 6.4 or higher based on actual sampling times.

50. Time to Last Quantifiable Concentration (Tlast) of the Blood Concentration of GSK1325756H for Part 1 [Pre-dose and at 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours in all 3 periods; 60 and 72 hours post-dose in period-3 of Part 1]

    Blood samples were collected at the indicated time points after administration of study treatment to investigate the PK profile of GSK1325756H in fasted state. PK parameters were calculated by standard non-compartmental analysis using Phoenix WinNonlin Version 6.4 or higher based on actual sampling times.

51. Cmax of GSK1325756H for Part 2 [Pre-dose and at 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours post-dose in Part 2]

    Blood samples were collected at the indicated time points after administration of study treatment to investigate the PK profile of GSK1325756H in fasted state. PK parameters were calculated by standard non-compartmental analysis using Phoenix WinNonlin Version 6.4 or higher based on actual sampling times.

52. AUC (0-t) of GSK1325756H for Part 2 [Pre-dose and at 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours post-dose in Part 2]

    Blood samples were collected at the indicated time points after administration of study treatment to investigate the PK profile of GSK1325756H in fasted state. PK parameters were calculated by standard non-compartmental analysis using Phoenix WinNonlin Version 6.4 or higher based on actual sampling times.

53. AUC (0-inf) of GSK1325756H for Part 2 [Pre-dose and at 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours post-dose in Part 2]

    Blood samples were collected at the indicated time points after administration of study treatment to investigate the PK profile of GSK1325756H in fasted state. PK parameters were calculated by standard non-compartmental analysis using Phoenix WinNonlin Version 6.4 or higher based on actual sampling times. Only those participants with data available at the indicated time points were analyzed.

54. AUC (0-24) of GSK1325756H for Part 2 [Pre-dose and at 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours post-dose in Part 2]

    Blood samples were collected at the indicated time points after administration of study treatment to investigate the PK profile of GSK1325756H in fasted state. PK parameters were calculated by standard non-compartmental analysis using Phoenix WinNonlin Version 6.4 or higher based on actual sampling times.

55. Tmax of GSK1325756H for Part 2 [Pre-dose and at 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours post-dose in Part 2]

    Blood samples were collected at the indicated time points after administration of study treatment to investigate the PK profile of GSK1325756H in fasted state. PK parameters were calculated by standard non-compartmental analysis using Phoenix WinNonlin Version 6.4 or higher based on actual sampling times.

56. t1/2 of GSK1325756H for Part 2 [Pre-dose and at 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours post-dose in Part 2]

    Blood samples were collected at the indicated time points after administration of study treatment to investigate the PK profile of GSK1325756H in fasted state. PK parameters were calculated by standard non-compartmental analysis using Phoenix WinNonlin Version 6.4 or higher based on actual sampling times. Only those participants with data available at the indicated time points were analyzed.

57. Tlag of GSK1325756H for Part 2 [Pre-dose and at 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours post-dose in Part 2]

    Blood samples were collected at the indicated time points after administration of study treatment to investigate the PK profile of GSK1325756H in fasted state. PK parameters were calculated by standard non-compartmental analysis using Phoenix WinNonlin Version 6.4 or higher based on actual sampling times.

58. Tlast of the Blood Concentration of GSK1325756H for Part 2 [Pre-dose and at 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48 post-dose in Part 2]

    Blood samples were collected at the indicated time points after administration of study treatment to investigate the PK profile of GSK1325756H in fasted state. PK parameters were calculated by standard non-compartmental analysis using Phoenix WinNonlin Version 6.4 or higher based on actual sampling times.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 65 Years and Older
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: Yes

Inclusion Criteria

• Participant must be over 65 years of age inclusive, at the time of signing the informed consent.

• Participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and ECG. A subject with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or exclusion criteria, outside the reference range for the population being studied may be included only if the investigator in consultation with the Medical Monitor if required agree that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.

• Participants whose peripheral blood neutrophil counts and hematocrit values are within normal range at screening visit.

• Body weight >=50 kilogram (Kg) and body mass index (BMI) within the range 18.5-24.9 kg/square meter (m^2) (inclusive).

• Japanese Male: A male participant must agree to use contraception during the treatment period and until follow up visit.

• Capable of giving signed informed consent.

Exclusion Criteria

• History or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study treatment; or interfering with the interpretation of data.

• Abnormal blood pressure as determined by the investigator.

• Alanine Aminotransferase (ALT)>1.5x upper limit of normal (ULN).

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

• Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).

• QT interval corrected for heart rate according to Fridericia's formula (QTcF)> 450 millisecond (msec).

• Past or intended use of over-the-counter or prescription medication including herbal medications and proton pump inhibitor (PPI) within 14 days prior to dosing.

• History of donation of blood or blood products >=400 milliliter (mL) within 3 months or >=200 mL within 1 month prior to screening.

• Exposure to more than 4 new chemical entities within 12 months prior to the first dosing day.

• Current enrolment or past participation within the last 30 days before signing of consent in this clinical study involving an investigational study treatment or any other type of medical research.

• The subject with positive Serological test for syphilis (Rapid Plasma Reagin [RPR] and Treponema pallidum hemagglutination test [TPHA]), Human immunodeficiency virus (HIV) Antigen/Antibody, Hepatitis B surface antigen (HBsAg), Hepatitis C virus (HCV) antibody, or Human T-cell lymphotropic virus type 1 (HTLV-1) antibody at screening.

• Positive pre-study drug screen.

• Regular alcohol consumption within 6 months prior to the study defined as: an average weekly intake of > 14 units for males. One unit is equivalent to 350 mL of beer, 150 mL of wine or 45 mL of 80 proof distilled spirits.

• Smoking or history or regular use of tobacco- or nicotine-containing products within 6 months prior to screening.

• Sensitivity to any of the study treatments, or components thereof, or drug or other allergy that, in the opinion of the investigator or medical monitor, contraindicates participation in the study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Tokyo		Japan	162-0053
2	GSK Investigational Site	Tokyo		Japan	162-00

Sponsors and Collaborators

• GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline
• Study Director: GSK Clinical Trials, GlaxoSmithKline (for GlaxoSmithKline; Human Genome Sciences Inc., a GSK Company; Sirtris, a GSK Company; Stiefel, a GSK Company; ViiV Healthcare)

Study Documents (Full-Text)

• Study Protocol - May 8, 2017
• Statistical Analysis Plan - Jul 11, 2017

More Information

Publications

None provided.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT03136380
• Other Study ID Numbers: 206817
• First Posted: May 2, 2017
• Last Update Posted: Apr 18, 2019
• Last Verified: Jan 1, 2019

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by GlaxoSmithKline: healthy Japanese subjects; CXCR2 inhibitor; Danirixin
• Additional relevant MeSH terms: Pulmonary Disease, Chronic Obstructive

Study Results

Participant Flow

Recruitment Details	This study was conducted at a single center in Tokyo, Japan from 10-May-2017 to 31-July-2017.
Pre-assignment Detail	A total of 147 participants were screened of which 113 were screen failures the reasons of which were investigator discretion (1), lost to follow-up (2) screened but enrollment target reached prior to enrollment (5) and did not met inclusion/exclusion criteria (105). A total of 18 participants in Part 1 and 16 in Part 2 were enrolled in the study.

Arm/Group Title	Part 1-GSK1325756H 10 mg Then GSK1325756H 50 mg Then Placebo	Part 1-GSK1325756H 10 mg Then Placebo Then GSK1325756H 100 mg	Part 1-Placebo Then GSK1325756H 50 mg Then GSK1325756H 100 mg	Part 2-GSK1325756H Fed Followed by Fasted	Part 2-GSK1325756H Fasted Followed by Fed
Arm/Group Description	Participants in this arm received GSK1325756H 10 milligrams (mg) in treatment period 1 followed by GSK1325756H 50 mg in treatment period 2 followed by placebo in treatment period 3. The treatment periods were separated were separated by a minimum of one-week washout period.	Participants in this arm received GSK1325756H 10 mg in treatment period 1 followed placebo in treatment period 2 followed by GSK1325756H 100 mg in treatment period 3. The treatment periods were separated were separated by a minimum of one-week washout period.	Participants in this arm received placebo in treatment period 1 followed by GSK1325756H 50 mg in treatment period 2 followed by GSK1325756H 100 mg in treatment period 3. The treatment periods were separated were separated by a minimum of one-week washout period.	Participants were randomized to receive GSK1325756H 50 mg (fed) in Period 1 followed by GSK1325756H (fasted) in Period 2 of Part 2. The treatment periods were separated were separated by a minimum of one-week washout period.	Participants were randomized to receive GSK1325756H 50 mg (fasted) in Period 1 followed by GSK1325756H (fed) in Period 2 of Part 2. The treatment periods were separated were separated by a minimum of one-week washout period.
Period Title: Part 1, Period 1 (3 Days)
STARTED	6	6	6	0	0
COMPLETED	6	6	6	0	0
NOT COMPLETED	0	0	0	0	0
Period Title: Part 1, Period 1 (3 Days)
STARTED	6	6	6	0	0
COMPLETED	6	6	6	0	0
NOT COMPLETED	0	0	0	0	0
Period Title: Part 1, Period 1 (3 Days)
STARTED	6	6	6	0	0
COMPLETED	6	6	6	0	0
NOT COMPLETED	0	0	0	0	0
Period Title: Part 1, Period 1 (3 Days)
STARTED	6	6	6	0	0
COMPLETED	6	5	6	0	0
NOT COMPLETED	0	1	0	0	0
Period Title: Part 1, Period 1 (3 Days)
STARTED	6	5	6	0	0
COMPLETED	6	5	6	0	0
NOT COMPLETED	0	0	0	0	0
Period Title: Part 1, Period 1 (3 Days)
STARTED	0	0	0	8	8
COMPLETED	0	0	0	8	8
NOT COMPLETED	0	0	0	0	0
Period Title: Part 1, Period 1 (3 Days)
STARTED	0	0	0	8	8
COMPLETED	0	0	0	8	8
NOT COMPLETED	0	0	0	0	0
Period Title: Part 1, Period 1 (3 Days)
STARTED	0	0	0	8	8
COMPLETED	0	0	0	8	8
NOT COMPLETED	0	0	0	0	0

Baseline Characteristics

Arm/Group Title	Part 1-Total Participants	Part 2-Total Participants	Total
Arm/Group Description	Participants received a single dose of GSK1325756H 10 mg (fed), GSK1325756 50 mg (fed), GSK1325756 100 mg (fed) and matching placebo in one of the three treatment periods in a crossover manner. The treatment periods were separated by a minimum of one-week washout period. The maximum duration of participation of participants, in Part 1 was 24 days.	Participants received a single dose of GSK1325756 50 mg (fed) and GSK1325756 50 mg (fasted) in one of the two treatment periods in a crossover manner. The treatment periods were separated by a minimum of one-week washout period. The maximum duration of participation of participants, in Part 2 was 13 days.	Total of all reporting groups
Overall Participants	18	16	34
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	70.0 (3.01)	69.3 (2.89)	69.6 (2.93)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	18 100%	16 100%	34 100%
Race/Ethnicity, Customized (Count of Participants)
Japanese/East Asian /South East Asian Heritage	18 100%	16 100%	34 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Any Adverse Event (AE) and Serious Adverse Events in Part 1
Description	AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect or is medically significant. Safety population comprised of all participants who took at least one dose of study treatment.
Time Frame	Up to 32 days in Part 1

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Part 1: Placebo (Fed)	Part 1: GSK1325756H 10 mg (Fed)	Part 1: GSK1325756H 50 mg (Fed)	Part 1: GSK1325756H 100 mg (Fed)
Arm/Group Description	Participants received matching placebo tablets via the oral route with food (fed state) and 240 milliliters of water in Part 1.	Participants received GSK1325756H 10 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 1.	Participants received GSK1325756H 50 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 1.	Participants received GSK1325756H 100 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 1.
Measure Participants	18	12	12	11
Any AE	1 5.6%	0 0%	0 0%	1 NaN
Any SAE	0 0%	0 0%	0 0%	0 NaN

2. Primary Outcome

Title	Number of Participants With Any Adverse Event (AE) and Serious Adverse Events in Part 2
Description	AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect or is medically significant
Time Frame	Up to 21 days in Part 2

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Part 2: GSK1325756H 50 mg (Fed)	Part 2: GSK1325756H 50 mg (Fasted)
Arm/Group Description	Participants received GSK1325756H 50 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 2.	Participants received GSK1325756H 50 mg tablets via the oral route without food (fasted state) and 240 milliliters of water in Part 2.
Measure Participants	16	16
Any AE	1 5.6%	0 0%
Any SAE	0 0%	0 0%

3. Primary Outcome

Title	Change From Baseline in Clinical Laboratory Parameters Calcium, Cholesterol, Chloride, Glucose, High Density Lipids (HDL) Cholesterol, Potassium, Low Density Lipids (LDL) Cholesterol,Sodium,Phosphorus,Triglycerides,Urea/Blood Urea Nitrogen (BUN) in Part 1
Description	Blood samples were collected for the assessment of chemistry parameters namely calcium, cholesterol, chloride, glucose, HDL cholesterol, potassium, LDL cholesterol, sodium, phosphorus, triglycerides, and urea/BUN results for Part 1. Baseline was defined as assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose-visit value from the Baseline value. Only those participants with data available at the specified time were analyzed (represented by n=x in the category titles).
Time Frame	Baseline and up to 72 hours in Part 1

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Part 1: Placebo (Fed)	Part 1: GSK1325756H 10 mg (Fed)	Part 1: GSK1325756H 50 mg (Fed)	Part 1: GSK1325756H 100 mg (Fed)
Arm/Group Description	Participants received matching placebo tablets via the oral route with food (fed state) and 240 milliliters of water in Part 1.	Participants received GSK1325756H 10 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 1.	Participants received GSK1325756H 50 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 1.	Participants received GSK1325756H 100 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 1.
Measure Participants	18	12	12	11
Calcium, 48 hours	-0.0208 (0.04617)	-0.0187 (0.04137)	0.0021 (0.05675)
Calcium, 72 hours	-0.0000 (0.06312)	-0.0318 (0.05124)
Cholesterol, 48 hours	0.0453 (0.36206)	0.0129 (0.30588)	0.1681 (0.53220)
Cholesterol, 72 hours	0.2241 (0.62379)	-0.0541 (0.37997)
Chloride, 48 hours	1.8 (1.11)	1.9 (1.83)	1.9 (1.44)
Chloride, 72 hours	1.8 (1.17)	1.5 (1.75)
Glucose, 48 hours	0.2452 (0.27852)	0.3516 (0.34246)	0.1619 (0.32580)
Glucose, 72 hours	0.2776 (0.16088)	0.1463 (0.38958)
HDL cholesterol, 48 hours	-0.1789 (0.16035)	-0.1702 (0.12302)	-0.1228 (0.13910)
HDL cholesterol, 72 hours	-0.1509 (0.11380)	-0.2304 (0.10753)
Potassium, 48 hours	0.04 (0.162)	0.11 (0.231)	0.28 (0.359)
Potassium, 72 hours	-0.17 (0.294)	0.07 (0.200)
LDL cholesterol, 48 hours	-0.0065 (0.35150)	0.0043 (0.26961)	0.0711 (0.44012)
LDL cholesterol, 72 hours	0.1896 (0.56007)	-0.0188 (0.36555)
Sodium, 48 hours	0.6 (1.00)	1.4 (2.07)	0.9 (1.08)
Sodium, 72 hours	1.0 (0.89)	1.1 (1.45)
Phosphorus, 48 hours	-0.1588 (0.12039)	-0.1399 (0.08525)	-0.1426 (0.09972)
Phosphorus, 72 hours	-0.0969 (0.05776)	-0.1262 (0.11041)
Triglycerides, 48 hours	0.6422 (0.31917)	0.4963 (0.36405)	0.5575 (0.38005)
Triglycerides, 72 hours	0.3823 (0.34016)	0.4910 (0.21744)
Urea/BUN, 48 hours	-0.7140 (0.79099)	-0.5355 (1.14422)	-0.1785 (0.95672)
Urea/BUN, 72 hours	-0.2975 (0.41735)	-0.5193 (0.96276)

4. Primary Outcome

Title	Change From Baseline in Clinical Chemistry Parameters Alkaline Phosphatase, Alanine Amino Transferase (ALT), Aspartate Amino Transferase (AST), Creatine Kinase, Gamma Glutamyl Transferase (GGT) and Lactate Dehydrogenase for Part 1
Description	Blood samples were collected for the assessment of chemistry parameters namely alkaline phosphatase, ALT, AST, creatine kinase, GGT and lactate dehydrogenase for Part 1. Baseline was defined as assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose-visit value from the Baseline value. Only those participants with data available at the specified time were analyzed (represented by n=x in the category titles).
Time Frame	Baseline and up to 72 hours in Part 1

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Part 1: Placebo (Fed)	Part 1: GSK1325756H 10 mg (Fed)	Part 1: GSK1325756H 50 mg (Fed)	Part 1: GSK1325756H 100 mg (Fed)
Arm/Group Description	Participants received matching placebo tablets via the oral route with food (fed state) and 240 milliliters of water in Part 1.	Participants received GSK1325756H 10 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 1.	Participants received GSK1325756H 50 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 1.	Participants received GSK1325756H 100 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 1.
Measure Participants	18	12	12	11
Alkaline phosphatase, 48 hours	1.1 (9.08)	-1.5 (8.44)	0.0 (9.55)
Alkaline phosphatase,72 hours	12.5 (13.37)	4.6 (12.14)
ALT, 48 hours	-2.2 (2.89)	-0.5 (3.92)	-1.9 (2.94)
ALT, 72 hours	2.5 (3.83)	0.6 (2.29)
AST, 48 hours	-2.3 (4.38)	-0.6 (4.52)	-2.2 (3.19)
AST, 72 hours	1.5 (3.67)	-1.4 (2.11)
Creatine kinase, 48 hours	-29.0 (27.10)	-34.3 (23.83)	-32.3 (22.18)
Creatine kinase, 72 hours	-34.7 (9.99)	-46.4 (32.96)
GGT, 48 hours	-1.0 (1.48)	0.9 (1.44)	-1.9 (2.35)
GGT, 72 hours	2.0 (1.10)	-0.1 (1.70)
Lactate dehydrogenase, 48 hours	-15.3 (20.20)	-13.8 (11.66)	-12.0 (10.08)
Lactate dehydrogenase, 72 hours	-2.8 (49.15)	-17.3 (7.40)

5. Primary Outcome

Title	Change From Baseline in Clinical Chemistry Parameters Albumin and Total Protein for Part 1
Description	Blood samples were collected for the assessment of chemistry parameters namely albumin and total protein for Part 1. Baseline was defined as assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose-visit value from the Baseline value. Only those participants with data available at the specified time were analyzed (represented by n=x in the category titles).
Time Frame	Baseline and up to 72 hours in Part 1

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Part 1: Placebo (Fed)	Part 1: GSK1325756H 10 mg (Fed)	Part 1: GSK1325756H 50 mg (Fed)	Part 1: GSK1325756H 100 mg (Fed)
Arm/Group Description	Participants received matching placebo tablets via the oral route with food (fed state) and 240 milliliters of water in Part 1.	Participants received GSK1325756H 10 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 1.	Participants received GSK1325756H 50 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 1.	Participants received GSK1325756H 100 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 1.
Measure Participants	18	12	12	11
Albumin, 48 hours	-0.3 (1.44)	-0.6 (1.44)	0.3 (1.96)
Albumin, 72 hours	1.2 (2.32)	-1.0 (1.34)
Total protein, 48 hours	0.2 (2.59)	-0.3 (1.82)	0.8 (3.01)
Total protein, 72 hours	1.8 (2.64)	0.0 (2.49)

6. Primary Outcome

Title	Change From Baseline in Clinical Chemistry Parameters Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid for Part 1
Description	Blood samples were collected for the assessment of chemistry parameters namely direct bilirubin, total bilirubin, creatinine and uric acid for Part 1. Baseline was defined as assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose-visit value from the Baseline value. Only those participants with data available at the specified time were analyzed (represented by n=x in the category titles).
Time Frame	Baseline and up to 72 hours in Part 1

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Part 1: Placebo (Fed)	Part 1: GSK1325756H 10 mg (Fed)	Part 1: GSK1325756H 50 mg (Fed)	Part 1: GSK1325756H 100 mg (Fed)
Arm/Group Description	Participants received matching placebo tablets via the oral route with food (fed state) and 240 milliliters of water in Part 1.	Participants received GSK1325756H 10 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 1.	Participants received GSK1325756H 50 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 1.	Participants received GSK1325756H 100 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 1.
Measure Participants	18	12	12	11
Direct bilirubin, 48 hours	-0.428 (0.7734)	0.000 (1.2629)	-0.712 (0.8805)
Direct bilirubin, 72 hours	-0.855 (1.4307)	-0.466 (0.7987)
Total bilirubin, 48 hours	-1.283 (2.0784)	-0.428 (3.3513)	-1.425 (1.9060)
Total bilirubin, 72 hours	-2.565 (4.6830)	-2.332 (1.7560)
Creatinine, 48 hours	-1.9890 (4.33275)	-3.6833 (3.21689)	-1.8417 (3.02629)
Creatinine, 72 hours	-4.7147 (3.73658)	-4.0985 (3.79755)
Uric acid, 48 hours	-33.7053 (25.78160)	-33.7053 (17.26380)	-31.7227 (21.57043)
Uric acid, 72 hours	-27.7573 (43.97767)	-23.2513 (23.10621)

7. Primary Outcome

Title	Change From Baseline in Clinical Chemistry Parameter Amylase for Part 1
Description	Blood samples were collected for the assessment of chemistry parameters namely amylase for Part 1. Baseline was defined as assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose-visit value from the Baseline value. Only those participants with data available at the specified time were analyzed (represented by n=x in the category titles).
Time Frame	Baseline and up to 72 hours in Part 1

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Part 1: Placebo (Fed)	Part 1: GSK1325756H 10 mg (Fed)	Part 1: GSK1325756H 50 mg (Fed)	Part 1: GSK1325756H 100 mg (Fed)
Arm/Group Description	Participants received matching placebo tablets via the oral route with food (fed state) and 240 milliliters of water in Part 1.	Participants received GSK1325756H 10 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 1.	Participants received GSK1325756H 50 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 1.	Participants received GSK1325756H 100 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 1.
Measure Participants	18	12	12	11
Amylase, 48 hours	16.0 (9.16)	20.6 (18.05)	22.7 (13.21)
Amylase, 72 hours	38.8 (28.84)	14.4 (12.92)

8. Primary Outcome

Title	Change From Baseline in Clinical Laboratory Parameters Calcium, Cholesterol, Chloride, Glucose, HDL Cholesterol, Potassium, LDL Cholesterol, Sodium, Phosphorus Inorganic, Triglycerides, Urea/BUN for Part 2
Description	Blood samples were collected for the assessment of chemistry parameters namely calcium, cholesterol, chloride, glucose, HDL cholesterol, potassium, LDL cholesterol, sodium, phosphorus, triglycerides, urea/BUN results for Part 2. Baseline was defined as assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose-visit value from the Baseline value.
Time Frame	Baseline and up to 48 hours in Part 2

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Part 2: GSK1325756H 50 mg (Fed)	Part 2: GSK1325756H 50 mg (Fasted)
Arm/Group Description	Participants received GSK1325756H 50 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 2.	Participants received GSK1325756H 50 mg tablets via the oral route without food (fasted state) and 240 milliliters of water in Part 2.
Measure Participants	16	16
Calcium, 48 hours	0.0000 (0.05834)	0.0000 (0.05154)
Cholesterol, 48 hours	0.3119 (0.37218)	0.3588 (0.25265)
Chloride, 48 hours	0.2 (2.01)	0.5 (1.86)
Glucose, 48 hours	0.2116 (0.23744)	0.1561 (0.35643)
HDL cholesterol, 48 hours	-0.1131 (0.12629)	-0.0808 (0.10678)
Potassium, 48 hours	0.18 (0.377)	0.14 (0.326)
LDL cholesterol, 48 hours	0.1729 (0.30124)	0.2279 (0.27614)
Sodium, 48 hours	-0.3 (1.65)	0.8 (1.72)
Phosphorus inorganic, 48 hours	-0.0868 (0.08561)	-0.1433 (0.08821)
Triglycerides, 48 hours	0.7402 (0.43390)	0.6010 (0.39556)
Urea/BUN, 48 hours	-0.6024 (1.44409)	-0.3347 (0.90755)

9. Primary Outcome

Title	Change From Baseline in Clinical Chemistry Parameters Alkaline Phosphatase, ALT, AST, Creatine Kinase, GGT and Lactate Dehydrogenase for Part 2
Description	Blood samples were collected for the assessment of chemistry parameters namely alkaline phosphatase, ALT, AST, creatine kinase, GGT and lactate dehydrogenase for Part 2. Baseline was defined as assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose-visit value from the Baseline value.
Time Frame	Baseline and up to 48 hours in Part 2

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Part 2: GSK1325756H 50 mg (Fed)	Part 2: GSK1325756H 50 mg (Fasted)
Arm/Group Description	Participants received GSK1325756H 50 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 2.	Participants received GSK1325756H 50 mg tablets via the oral route without food (fasted state) and 240 milliliters of water in Part 2.
Measure Participants	16	16
Alkaline phosphatase, 48 hours	0.9 (9.96)	6.5 (11.35)
ALT, 48 hours	-1.5 (1.93)	-1.5 (1.97)
AST, 48 hours	-2.0 (2.28)	-1.8 (1.29)
Creatine kinase, 48 hours	-29.7 (28.72)	-16.6 (18.89)
GGT, 48 hours	-0.5 (2.99)	-0.4 (2.50)
Lactate dehydrogenase, 48 hours	-14.8 (11.97)	-13.7 (6.80)

10. Primary Outcome

Title	Change From Baseline in Clinical Chemistry Parameters Albumin and Total Protein for Part 2
Description	Blood samples were collected for the assessment of chemistry parameters namely albumin and total protein for Part 2. Baseline was defined as assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose-visit value from the Baseline value.
Time Frame	Baseline and up to 48 hours in Part 2

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Part 2: GSK1325756H 50 mg (Fed)	Part 2: GSK1325756H 50 mg (Fasted)
Arm/Group Description	Participants received GSK1325756H 50 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 2.	Participants received GSK1325756H 50 mg tablets via the oral route without food (fasted state) and 240 milliliters of water in Part 2.
Measure Participants	16	16
Albumin, 48 hours	0.3 (1.54)	0.8 (1.48)
Total protein, 48 hours	1.1 (2.66)	1.9 (2.25)

11. Primary Outcome

Title	Change From Baseline in Clinical Chemistry Parameters Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid for Part 2
Description	Blood samples were collected for the assessment of chemistry parameters namely direct bilirubin, total bilirubin, creatinine and uric acid for Part 2. Baseline was defined as assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose-visit value from the Baseline value.
Time Frame	Baseline and up to 48 hours in Part 2

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Part 2: GSK1325756H 50 mg (Fed)	Part 2: GSK1325756H 50 mg (Fasted)
Arm/Group Description	Participants received GSK1325756H 50 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 2.	Participants received GSK1325756H 50 mg tablets via the oral route without food (fasted state) and 240 milliliters of water in Part 2.
Measure Participants	16	16
Direct bilirubin, 48 hours	-0.641 (1.5135)	-0.641 (1.2291)
Total bilirubin, 48 hours	-1.496 (4.6254)	-0.748 (2.6468)
Creatinine, 48 hours	-2.8178 (3.68348)	-4.2542 (3.32677)
Uric acid, 48 hours	-15.6135 (54.03085)	-8.5502 (75.89141)

12. Primary Outcome

Title	Change From Baseline in Clinical Chemistry Parameter Amylase for Part 2
Description	Blood samples were collected for the assessment of chemistry parameter namely amylase for Part 1. Baseline was defined as assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose-visit value from the Baseline value.
Time Frame	Baseline and up to 48 hours in Part 2

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Part 2: GSK1325756H 50 mg (Fed)	Part 2: GSK1325756H 50 mg (Fasted)
Arm/Group Description	Participants received GSK1325756H 50 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 2.	Participants received GSK1325756H 50 mg tablets via the oral route without food (fasted state) and 240 milliliters of water in Part 2.
Measure Participants	16	16
Mean (Standard Deviation) [Units/liter]	18.2 (8.63)	18.5 (8.75)

13. Primary Outcome

Title	Change From Baseline in Hematology Parameters Basophils, Eosinophils, Lymphocytes, Monocytes and Total Neutrophils for Part 1
Description	Blood samples were collected for the assessment of hematology parameters namely basophils, eosinophils, leukocytes, lymphocytes, monocytes, total neutrophils and platelets for Part 1. Baseline was defined as assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose-visit value from the Baseline value. Only those participants with data available at the specified time were analyzed (represented by n=x in the category titles).
Time Frame	Baseline and up to 72 hours in Part 1

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Part 1: Placebo (Fed)	Part 1: GSK1325756H 10 mg (Fed)	Part 1: GSK1325756H 50 mg (Fed)	Part 1: GSK1325756H 100 mg (Fed)
Arm/Group Description	Participants received matching placebo tablets via the oral route with food (fed state) and 240 milliliters of water in Part 1.	Participants received GSK1325756H 10 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 1.	Participants received GSK1325756H 50 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 1.	Participants received GSK1325756H 100 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 1.
Measure Participants	18	12	12	11
Basophils, 48 hours	0.12 (0.221)	0.09 (0.168)	0.09 (0.131)
Basophils, 72 hours	0.13 (0.082)	0.03 (0.272)
Eosinophils, 48 hours	1.39 (1.132)	0.95 (1.301)	0.73 (0.725)
Eosinophils, 72 hours	1.10 (1.753)	0.54 (0.923)
Lymphocytes, 48 hours	5.18 (4.754)	5.35 (5.907)	4.39 (4.019)
Lymphocytes, 72 hours	5.15 (3.363)	2.85 (7.766)
Monocytes, 48 hours	-0.13 (0.677)	0.01 (1.093)	-0.12 (0.920)
Monocytes, 72 hours	-0.18 (0.652)	0.16 (1.249)
Total neutrophils, 48 hours	-6.56 (5.347)	-6.40 (7.071)	-5.10 (4.611)
Total neutrophils, 72 hours	-6.20 (3.946)	-3.57 (9.212)

14. Primary Outcome

Title	Change From Baseline in Hematology Parameter Hemoglobin for Part 1
Description	Blood samples were collected for the assessment of hematology parameter namely hemoglobin for Part 1. Baseline was defined as assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose-visit value from the Baseline value. Only those participants with data available at the specified time were analyzed (represented by n=x in the category titles).
Time Frame	Baseline and up to 72 hours in Part 1

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Part 1: Placebo (Fed)	Part 1: GSK1325756H 10 mg (Fed)	Part 1: GSK1325756H 50 mg (Fed)	Part 1: GSK1325756H 100 mg (Fed)
Arm/Group Description	Participants received matching placebo tablets via the oral route with food (fed state) and 240 milliliters of water in Part 1.	Participants received GSK1325756H 10 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 1.	Participants received GSK1325756H 50 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 1.	Participants received GSK1325756H 100 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 1.
Measure Participants	18	12	12	11
Hemoglobin, 48 hours	3.7 (4.66)	4.8 (4.24)	5.5 (5.05)
Hemoglobin, 72 hours	8.8 (5.23)	5.0 (5.53)

15. Primary Outcome

Title	Change From Baseline in Hematology Parameter Hematocrit for Part 1
Description	Blood samples were collected for the assessment of hematology parameter namely hematocrit for Part 1. Baseline was defined as assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose-visit value from the Baseline value. Only those participants with data available at the specified time were analyzed (represented by n=x in the category titles).
Time Frame	Baseline and up to 72 hours in Part 1

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Part 1: Placebo (Fed)	Part 1: GSK1325756H 10 mg (Fed)	Part 1: GSK1325756H 50 mg (Fed)	Part 1: GSK1325756H 100 mg (Fed)
Arm/Group Description	Participants received matching placebo tablets via the oral route with food (fed state) and 240 milliliters of water in Part 1.	Participants received GSK1325756H 10 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 1.	Participants received GSK1325756H 50 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 1.	Participants received GSK1325756H 100 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 1.
Measure Participants	18	12	12	11
Hematocrit, 48 hours	0.0188 (0.01542)	0.0177 (0.01293)	0.0238 (0.01599)
Hematocrit, 72 hours	0.0255 (0.01472)	0.0121 (0.01700)

16. Primary Outcome

Title	Change From Baseline in Hematology Parameter Mean Corpuscle Hemoglobin for Part 1
Description	Blood samples were collected for the assessment of hematology parameter namely mean corpuscle hemoglobin for Part 1. Baseline was defined as assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose-visit value from the Baseline value. Only those participants with data available at the specified time were analyzed (represented by n=x in the category titles).
Time Frame	Baseline and up to 72 hours in Part 1

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Part 1: Placebo (Fed)	Part 1: GSK1325756H 10 mg (Fed)	Part 1: GSK1325756H 50 mg (Fed)	Part 1: GSK1325756H 100 mg (Fed)
Arm/Group Description	Participants received matching placebo tablets via the oral route with food (fed state) and 240 milliliters of water in Part 1.	Participants received GSK1325756H 10 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 1.	Participants received GSK1325756H 50 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 1.	Participants received GSK1325756H 100 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 1.
Measure Participants	18	12	12	11
Mean corpuscle hemoglobin, 48 hours	-0.32 (0.376)	-0.10 (0.429)	-0.14 (0.306)
Mean corpuscle hemoglobin, 72 hours	0.22 (0.479)	0.25 (0.362)

17. Primary Outcome

Title	Change From Baseline in Hematology Parameter Mean Corpuscle Volume for Part 1
Description	Blood samples were collected for the assessment of hematology parameter namely mean corpuscle volume for Part 1. Baseline was defined as assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose-visit value from the Baseline value. Only those participants with data available at the specified time were analyzed (represented by n=x in the category titles).
Time Frame	Baseline and up to 72 hours in Part 1

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Part 1: Placebo (Fed)	Part 1: GSK1325756H 10 mg (Fed)	Part 1: GSK1325756H 50 mg (Fed)	Part 1: GSK1325756H 100 mg (Fed)
Arm/Group Description	Participants received matching placebo tablets via the oral route with food (fed state) and 240 milliliters of water in Part 1.	Participants received GSK1325756H 10 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 1.	Participants received GSK1325756H 50 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 1.	Participants received GSK1325756H 100 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 1.
Measure Participants	18	12	12	11
Mean corpuscle volume, 48 hours	0.7 (0.78)	0.3 (0.65)	1.3 (0.87)
Mean corpuscle volume, 72 hours	0.2 (0.75)	0.2 (0.75)

18. Primary Outcome

Title	Change From Baseline in Hematology Parameters Platelet Count and White Blood Cell Count for Part 1
Description	Blood samples were collected for the assessment of hematology parameters namely platelet count and white blood cell count for Part 1. Baseline was defined as assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose-visit value from the Baseline value. Only those participants with data available at the specified time were analyzed (represented by n=x in the category titles).
Time Frame	Baseline and up to 72 hours in Part 1

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Part 1: Placebo (Fed)	Part 1: GSK1325756H 10 mg (Fed)	Part 1: GSK1325756H 50 mg (Fed)	Part 1: GSK1325756H 100 mg (Fed)
Arm/Group Description	Participants received matching placebo tablets via the oral route with food (fed state) and 240 milliliters of water in Part 1.	Participants received GSK1325756H 10 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 1.	Participants received GSK1325756H 50 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 1.	Participants received GSK1325756H 100 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 1.
Measure Participants	18	12	12	11
Platelet count, 48 hours	3.7 (14.59)	1.4 (12.55)	0.5 (15.95)
Platelet count, 72 hours	14.5 (11.33)	2.3 (10.53)
White blood cell count,48 hours	-0.54 (0.489)	-0.48 (0.956)	-0.67 (0.947)
White blood cell count,72 hours	-0.32 (0.471)	-0.75 (1.258)

19. Primary Outcome

Title	Change From Baseline in Hematology Parameters Red Blood Count and Reticulocyte Count for Part 1
Description	Blood samples were collected for the assessment of hematology parameters namely red blood count and reticulocyte count for Part 1. Baseline was defined as assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose-visit value from the Baseline value. Only those participants with data available at the specified time were analyzed (represented by n=x in the category titles).
Time Frame	Baseline and up to 72 hours in Part 1

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Part 1: Placebo (Fed)	Part 1: GSK1325756H 10 mg (Fed)	Part 1: GSK1325756H 50 mg (Fed)	Part 1: GSK1325756H 100 mg (Fed)
Arm/Group Description	Participants received matching placebo tablets via the oral route with food (fed state) and 240 milliliters of water in Part 1.	Participants received GSK1325756H 10 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 1.	Participants received GSK1325756H 50 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 1.	Participants received GSK1325756H 100 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 1.
Measure Participants	18	12	12	11
Red blood cell count, 48 hours	0.165 (0.1650)	0.164 (0.1385)	0.197 (0.1797)
Red blood cell count, 72 hours	0.252 (0.1609)	0.120 (0.1680)
Reticulocyte count, 48 hours	0.0127 (0.01512)	0.0038 (0.01765)	-0.0009 (0.01929)
Reticulocyte count, 72 hours	-0.0023 (0.01646)	-0.0037 (0.01780)

20. Primary Outcome

Title	Change From Baseline in Hematology Parameters Basophils, Eosinophils, Lymphocytes, Monocytes and Total Neutrophils for Part 2
Description	Blood samples were collected for the assessment of hematology parameters namely basophils, eosinophils, leukocytes, lymphocytes, monocytes, total neutrophils and platelets for Part 2. Baseline was defined as assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose-visit value from the Baseline value.
Time Frame	Baseline and up to 48 hours in Part 2

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Part 2: GSK1325756H 50 mg (Fed)	Part 2: GSK1325756H 50 mg (Fasted)
Arm/Group Description	Participants received GSK1325756H 50 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 2.	Participants received GSK1325756H 50 mg tablets via the oral route without food (fasted state) and 240 milliliters of water in Part 2.
Measure Participants	16	16
Basophils, 48 hours	-0.00 (0.250)	0.09 (0.120)
Eosinophils, 48 hours	0.44 (1.082)	0.67 (0.960)
Lymphocytes, 48 hours	3.58 (7.821)	4.53 (5.248)
Monocytes, 48 hours	-0.04 (0.873)	-0.63 (0.936)
Total neutrophils, 48 hours	-3.97 (9.311)	-4.66 (6.035)

21. Primary Outcome

Title	Change From Baseline in Hematology Parameter Hemoglobin for Part 2
Description	Blood samples were collected for the assessment of hematology parameter namely hemoglobin for Part 2. Baseline was defined as assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose-visit value from the Baseline value.
Time Frame	Baseline and up to 48 hours in Part 2

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Part 2: GSK1325756H 50 mg (Fed)	Part 2: GSK1325756H 50 mg (Fasted)
Arm/Group Description	Participants received GSK1325756H 50 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 2.	Participants received GSK1325756H 50 mg tablets via the oral route without food (fasted state) and 240 milliliters of water in Part 2.
Measure Participants	16	16
Mean (Standard Deviation) [Grams/liter]	9.4 (3.92)	8.9 (4.51)

22. Primary Outcome

Title	Change From Baseline in Hematology Parameter Hematocrit for Part 2
Description	Blood samples were collected for the assessment of hematology parameter namely hematocrit for Part 2. Baseline was defined as assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose-visit value from the Baseline value.
Time Frame	Baseline and up to 48 hours in Part 2

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Part 2: GSK1325756H 50 mg (Fed)	Part 2: GSK1325756H 50 mg (Fasted)
Arm/Group Description	Participants received GSK1325756H 50 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 2.	Participants received GSK1325756H 50 mg tablets via the oral route without food (fasted state) and 240 milliliters of water in Part 2.
Measure Participants	16	16
Mean (Standard Deviation) [Proportion of red blood cells in blood]	0.0304 (0.01286)	0.0268 (0.01303)

23. Primary Outcome

Title	Change From Baseline in Hematology Parameter Mean Corpuscle Hemoglobin for Part 2
Description	Blood samples were collected for the assessment of hematology parameter namely mean corpuscle hemoglobin for Part 2. Baseline was defined as assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose-visit value from the Baseline value.
Time Frame	Baseline and up to 48 hours in Part 2

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Part 2: GSK1325756H 50 mg (Fed)	Part 2: GSK1325756H 50 mg (Fasted)
Arm/Group Description	Participants received GSK1325756H 50 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 2.	Participants received GSK1325756H 50 mg tablets via the oral route without food (fasted state) and 240 milliliters of water in Part 2.
Measure Participants	16	16
Mean (Standard Deviation) [Picograms]	-0.12 (0.312)	0.20 (0.268)

24. Primary Outcome

Title	Change From Baseline in Hematology Parameter Mean Corpuscle Volume for Part 2
Description	Blood samples were collected for the assessment of hematology parameter namely mean corpuscle volume for Part 2. Baseline was defined as assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose-visit value from the Baseline value.
Time Frame	Baseline and up to 48 hours in Part 2

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Part 2: GSK1325756H 50 mg (Fed)	Part 2: GSK1325756H 50 mg (Fasted)
Arm/Group Description	Participants received GSK1325756H 50 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 2.	Participants received GSK1325756H 50 mg tablets via the oral route without food (fasted state) and 240 milliliters of water in Part 2.
Measure Participants	16	16
Mean (Standard Deviation) [Femtoliters]	0.4 (0.96)	0.6 (0.89)

25. Primary Outcome

Title	Change From Baseline in Hematology Parameters Platelet Count and White Blood Cell Count for Part 2
Description	Blood samples were collected for the assessment of hematology parameters namely platelet count and white blood cell count for Part 2. Baseline was defined as assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose-visit value from the Baseline value.
Time Frame	Baseline and up to 48 hours in Part 2

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Part 2: GSK1325756H 50 mg (Fed)	Part 2: GSK1325756H 50 mg (Fasted)
Arm/Group Description	Participants received GSK1325756H 50 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 2.	Participants received GSK1325756H 50 mg tablets via the oral route without food (fasted state) and 240 milliliters of water in Part 2.
Measure Participants	16	16
Platelet count, 48 hours	7.4 (15.32)	13.1 (12.45)
White blood cell count,48 hours	12.45 (0.995)	-0.36 (0.734)

26. Primary Outcome

Title	Change From Baseline in Hematology Parameters Red Blood Count and Reticulocyte Count for Part 2
Description	Blood samples were collected for the assessment of hematology parameters namely red blood count and reticulocyte count for Part 2. Baseline was defined as assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose-visit value from the Baseline value.
Time Frame	Baseline and up to 48 hours in Part 2

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Part 2: GSK1325756H 50 mg (Fed)	Part 2: GSK1325756H 50 mg (Fasted)
Arm/Group Description	Participants received GSK1325756H 50 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 2.	Participants received GSK1325756H 50 mg tablets via the oral route without food (fasted state) and 240 milliliters of water in Part 2.
Measure Participants	16	16
Red blood cell count, 48 hours	0.318 (0.1462)	0.255 (0.1590)
Reticulocyte count, 48 hours	-0.0018 (0.01203)	0.0097 (0.01526)

27. Primary Outcome

Title	Number of Participants With Abnormal Values on Urinalysis by Dipstick Method for Part 1
Description	Urinalysis parameters assessed were urine bilirubin, urine occult blood, urine glucose, urine ketones, urine protein and urine urobilinogen. In this dipstick test, the level of bilirubin, occult blood, glucose, ketones, urine protein and urobilinogen in urine samples was recorded as negative, trace and +. Urine samples were collected for the measurement of urinalysis parameters by dipstick method up to 72 hours in Part 1. Only categories with significant values have been presented.
Time Frame	Up to 72 hours in Part 1

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Part 1: Placebo (Fed)	Part 1: GSK1325756H 10 mg (Fed)	Part 1: GSK1325756H 50 mg (Fed)	Part 1: GSK1325756H 100 mg (Fed)
Arm/Group Description	Participants received matching placebo tablets via the oral route with food (fed state) and 240 milliliters of water in Part 1.	Participants received GSK1325756H 10 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 1.	Participants received GSK1325756H 50 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 1.	Participants received GSK1325756H 100 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 1.
Measure Participants	18	12	12	11
Urine occult blood, Trace, 48 hours	1 5.6%	1 6.3%	0 0%	0 NaN
Urine occult blood, + , 48 hours	0 0%	1 6.3%	1 2.9%	0 NaN
Urine occult blood, Trace, 72 hours	1 5.6%	0 0%	0 0%	0 NaN
Urine occult blood, + , 72 hours	1 5.6%	0 0%	0 0%	0 NaN
Urine protein, Trace, 48 hours	0 0%	1 6.3%	1 2.9%	0 NaN
Urine protein, Trace, 72 hours	1 5.6%	0 0%	0 0%	0 NaN
Urine urobilinogen, Trace, 48 hours	12 66.7%	12 75%	12 35.3%	0 NaN
Urine urobilinogen, Trace, 72 hours	6 33.3%	0 0%	0 0%	11 NaN

28. Primary Outcome

Title	Urine Potential of Hydrogen (pH) Analysis by Dipstick Method for Part 1
Description	Urinary pH measurement is a routine part of urinalysis. Urine pH is an acid-base measurement. pH is measured on a numeric scale ranging from 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). Urine samples were collected for the measurement of urine pH by method up to 72 hours in Part 1. Only those participants with data available at the specified time were analyzed (represented by n=x in the category titles).
Time Frame	Up to 72 hours in Part 1

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Part 1: Placebo (Fed)	Part 1: GSK1325756H 10 mg (Fed)	Part 1: GSK1325756H 50 mg (Fed)	Part 1: GSK1325756H 100 mg (Fed)
Arm/Group Description	Participants received matching placebo tablets via the oral route with food (fed state) and 240 milliliters of water in Part 1.	Participants received GSK1325756H 10 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 1.	Participants received GSK1325756H 50 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 1.	Participants received GSK1325756H 100 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 1.
Measure Participants	18	12	12	11
Urine pH, 48 hours	6.42 (0.634)	6.17 (0.389)	6.42 (0.469)
Urine pH, 72 hours	6.08 (0.492)	6.36 (0.636)

29. Primary Outcome

Title	Urine Specific Gravity Analysis by Dipstick Method for Part 1
Description	Urinary specific gravity measurement is a routine part of urinalysis. Urine specific gravity is a measure of the concentration of solutes in the urine and provides information on the kidney's ability to concentrate urine. The concentration of the excreted molecules determines the urine's specific gravity. Urine samples were collected for the measurement of urine specific gravity by dipstick method up to 72 hours in Part 1. Only those participants with data available at the specified time were analyzed (represented by n=x in the category titles). Density is the mass per unit volume and has units (such as g/cm^3), however, the specific gravity is a ratio so it has no unit.
Time Frame	Up to 72 hours in Part 1

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Part 1: Placebo (Fed)	Part 1: GSK1325756H 10 mg (Fed)	Part 1: GSK1325756H 50 mg (Fed)	Part 1: GSK1325756H 100 mg (Fed)
Arm/Group Description	Participants received matching placebo tablets via the oral route with food (fed state) and 240 milliliters of water in Part 1.	Participants received GSK1325756H 10 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 1.	Participants received GSK1325756H 50 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 1.	Participants received GSK1325756H 100 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 1.
Measure Participants	18	12	12	11
Mean (Standard Deviation) [Ratio]	1.0167 (0.00753)	NA (NA)	NA (NA)	1.0150 (0.00224)

30. Primary Outcome

Title	Number of Participants With Abnormal Values on Urinalysis by Dipstick Method for Part 2
Description	Urinalysis parameters assessed were urine bilirubin, urine occult blood, urine glucose, urine ketones, urine protein and urine urobilinogen. In this dipstick test, the level of bilirubin, occult blood, glucose, ketones, urine protein and urobilinogen in urine samples was recorded as negative, trace and +. Urine samples were collected for the measurement of urinalysis parameters by dipstick method up to 48 hours in Part 2. Only categories with significant values have been presented.
Time Frame	Up to 48 hours in Part 2

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Part 2: GSK1325756H 50 mg (Fed)	Part 2: GSK1325756H 50 mg (Fasted)
Arm/Group Description	Participants received GSK1325756H 50 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 2.	Participants received GSK1325756H 50 mg tablets via the oral route without food (fasted state) and 240 milliliters of water in Part 2.
Measure Participants	16	16
Urine occult blood, Trace, 48 hours	1 5.6%	0 0%
Urine glucose, Trace , 48 hours	1 5.6%	0 0%
Urine protein, Trace, 48 hours	0 0%	2 12.5%
Urine urobilinogen, Trace, 48 hours	15 83.3%	15 93.8%
Urine urobilinogen, +, 48 hours	1 5.6%	1 6.3%

31. Primary Outcome

Title	Urine pH Analysis by Dipstick Method for Part 2
Description	Urinary pH measurement is a routine part of urinalysis. Urine pH is an acid-base measurement. pH is measured on a numeric scale ranging from 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). Urine samples were collected for the measurement of urine pH by dipstick method up to 48 hours in Part 2.
Time Frame	Up to 48 hours in Part 2

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Part 2: GSK1325756H 50 mg (Fed)	Part 2: GSK1325756H 50 mg (Fasted)
Arm/Group Description	Participants received GSK1325756H 50 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 2.	Participants received GSK1325756H 50 mg tablets via the oral route without food (fasted state) and 240 milliliters of water in Part 2.
Measure Participants	16	16
Mean (Standard Deviation) [pH]	6.66 (0.724)	6.47 (0.718)

32. Primary Outcome

Title	Urine Specific Gravity Analysis by Dipstick Method for Part 2
Description	Urinary specific gravity measurement is a routine part of urinalysis. Urine specific gravity is a measure of the concentration of solutes in the urine and provides information on the kidney's ability to concentrate urine. The concentration of the excreted molecules determines the urine's specific gravity. Urine samples were collected for the measurement of urine specific gravity by dipstick method up to 48 hours in Part 2. Density is the mass per unit volume and has units (such as g/cm^3), however, the specific gravity is a ratio so it has no unit.
Time Frame	Up to 72 hours in Part 2

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Part 2: GSK1325756H 50 mg (Fed)	Part 2: GSK1325756H 50 mg (Fasted)
Arm/Group Description	Participants received GSK1325756H 50 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 2.	Participants received GSK1325756H 50 mg tablets via the oral route without food (fasted state) and 240 milliliters of water in Part 2.
Measure Participants	16	16
Mean (Standard Deviation) [Ratio]	1.0153 (0.00618)	1.0159 (0.00712)

33. Primary Outcome

Title	Change From Baseline in Vital Sign Parameters Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) for Part 1
Description	Vital sign measurements included SBP and DBP at Baseline and up to 72 hours in Part 1. SBP and DBP measurements were preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions and were measured in a supine position after 5 minutes rest. Baseline was defined as pre-dose assessments performed on Day 1. Change from Baseline was calculated by subtracting the post-dose-visit value from the Baseline value. Only those participants with data available at the specified time were analyzed (represented by n=x in the category titles).
Time Frame	Baseline and up to 72 hours in Part 1

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Part 1: Placebo (Fed)	Part 1: GSK1325756H 10 mg (Fed)	Part 1: GSK1325756H 50 mg (Fed)	Part 1: GSK1325756H 100 mg (Fed)
Arm/Group Description	Participants received matching placebo tablets via the oral route with food (fed state) and 240 milliliters of water in Part 1.	Participants received GSK1325756H 10 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 1.	Participants received GSK1325756H 50 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 1.	Participants received GSK1325756H 100 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 1.
Measure Participants	18	12	12	11
SBP, 4 hours	-4.8 (10.44)	-9.6 (9.21)	-4.2 (6.59)	-0.3 (7.02)
SBP, 24 hours	1.7 (7.95)	0.5 (13.61)	1.7 (6.87)	4.5 (13.55)
SBP, 48 hours	4.5 (7.06)	7.0 (10.76)	5.9 (11.66)	2.0 (10.47)
SBP, 72 hours	-0.8 (8.06)	4.8 (12.18)
DBP, 4 hours	-3.6 (5.89)	-2.8 (3.33)	-2.2 (4.93)	-1.1 (5.36)
DBP, 24 hours	0.8 (4.94)	4.5 (4.58)	0.8 (6.40)	1.0 (6.32)
DBP, 48 hours	2.0 (6.24)	4.7 (6.07)	2.1 (4.44)	2.5 (6.12)
DBP, 72 hours	3.8 (4.12)	1.8 (7.69)

34. Primary Outcome

Title	Change From Baseline in Vital Sign Parameter Heart Rate for Part 1
Description	Vital sign measurements included heart rate at Baseline and up to 72 hours in Part 1. Heart rate measurements were preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions and were measured in a supine position after 5 minutes rest. Baseline was defined as pre-dose assessments performed on Day 1. Change from Baseline was calculated by subtracting the post-dose-visit value from the Baseline value. Only those participants with data available at the specified time were analyzed (represented by n=x in the category titles).
Time Frame	Baseline and up to 72 hours in Part 1

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Part 1: Placebo (Fed)	Part 1: GSK1325756H 10 mg (Fed)	Part 1: GSK1325756H 50 mg (Fed)	Part 1: GSK1325756H 100 mg (Fed)
Arm/Group Description	Participants received matching placebo tablets via the oral route with food (fed state) and 240 milliliters of water in Part 1.	Participants received GSK1325756H 10 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 1.	Participants received GSK1325756H 50 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 1.	Participants received GSK1325756H 100 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 1.
Measure Participants	18	12	12	11
Heart rate, 4 hours	-3.1 (3.92)	-3.2 (8.24)	-3.7 (6.17)	-2.9 (2.95)
Heart rate, 24 hours	-3.0 (4.67)	-7.5 (9.23)	-3.8 (4.97)	-2.2 (4.07)
Heart rate, 48 hours	-1.5 (3.09)	1.2 (7.51)	-2.3 (6.59)	-2.7 (4.31)
Heart rate, 72 hours	-1.0 (4.98)	-1.0 (5.14)

35. Primary Outcome

Title	Change From Baseline in Vital Sign Parameter Temperature for Part 1
Description	Vital sign measurements included temperature at Baseline and up to 72 hours in Part 1. Temperature measurements were preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions and were measured in a supine position after 5 minutes rest. Baseline was defined as pre-dose assessments performed on Day 1. Change from Baseline was calculated by subtracting the post-dose-visit value from the Baseline value. Only those participants with data available at the specified time were analyzed (represented by n=x in the category titles).
Time Frame	Baseline and up to 72 hours in Part 1

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Part 1: Placebo (Fed)	Part 1: GSK1325756H 10 mg (Fed)	Part 1: GSK1325756H 50 mg (Fed)	Part 1: GSK1325756H 100 mg (Fed)
Arm/Group Description	Participants received matching placebo tablets via the oral route with food (fed state) and 240 milliliters of water in Part 1.	Participants received GSK1325756H 10 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 1.	Participants received GSK1325756H 50 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 1.	Participants received GSK1325756H 100 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 1.
Measure Participants	18	12	12	11
Temperature, 4 hours	0.11 (0.363)	0.07 (0.400)	0.27 (0.393)	0.14 (0.495)
Temperature 24 hours	-0.08 (0.269)	0.01 (0.375)	0.06 (0.394)	0.05 (0.321)
Temperature, 48 hours	0.02 (0.362)	-0.02 (0.364)	0.01 (0.387)	0.12 (0.460)
Temperature, 72 hours	0.00 (0.179)	0.17 (0.272)

36. Primary Outcome

Title	Change From Baseline in Vital Sign Parameters SBP and DBP for Part 2
Description	Vital sign measurements included SBP and DBP at Baseline and up to 72 hours in Part 2. SBP and DBP measurements were preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions and were measured in a supine position after 5 minutes rest. Baseline was defined as pre-dose assessments performed on Day 1. Change from Baseline was calculated by subtracting the post-dose-visit value from the Baseline value.
Time Frame	Baseline and up to 48 hours in Part 2

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Part 2: GSK1325756H 50 mg (Fed)	Part 2: GSK1325756H 50 mg (Fasted)
Arm/Group Description	Participants received GSK1325756H 50 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 2.	Participants received GSK1325756H 50 mg tablets via the oral route without food (fasted state) and 240 milliliters of water in Part 2.
Measure Participants	16	16
SBP, 4 hours	-1.5 (11.70)	-2.5 (12.46)
SBP, 24 hours	-2.8 (12.13)	-3.5 (11.64)
SBP, 48 hours	-1.9 (10.22)	-0.2 (14.47)
DBP, 4 hours	-0.8 (6.19)	-0.3 (6.63)
DBP, 24 hours	-0.7 (6.66)	-0.6 (6.15)
DBP, 48 hours	0.1 (3.80)	0.8 (6.31)

37. Primary Outcome

Title	Change From Baseline in Vital Sign Parameter Heart Rate for Part 2
Description	Vital sign measurements included heart rate at Baseline and up to 72 hours in Part 2. Heart rate measurements were preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions and were measured in a supine position after 5 minutes rest. Baseline was defined as pre-dose assessments performed on Day 1. Change from Baseline was calculated by subtracting the post-dose-visit value from the Baseline value.
Time Frame	Baseline and up to 48 hours in Part 2

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Part 2: GSK1325756H 50 mg (Fed)	Part 2: GSK1325756H 50 mg (Fasted)
Arm/Group Description	Participants received GSK1325756H 50 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 2.	Participants received GSK1325756H 50 mg tablets via the oral route without food (fasted state) and 240 milliliters of water in Part 2.
Measure Participants	16	16
Heart rate, 4 hours	-2.4 (4.69)	-1.8 (5.14)
Heart rate, 24 hours	1.3 (5.46)	-0.1 (3.89)
Heart rate, 48 hours	0.5 (3.83)	0.5 (4.07)

38. Primary Outcome

Title	Change From Baseline in Vital Sign Parameter Temperature for Part 2
Description	Vital sign measurements included temperature at Baseline and up to 72 hours in Part 2. Temperature measurements were preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions and were measured in a supine position after 5 minutes rest. Baseline was defined as pre-dose assessments performed on Day 1. Change from Baseline was calculated by subtracting the post-dose-visit value from the Baseline value.
Time Frame	Baseline and up to 48 hours in Part 2

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Part 2: GSK1325756H 50 mg (Fed)	Part 2: GSK1325756H 50 mg (Fasted)
Arm/Group Description	Participants received GSK1325756H 50 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 2.	Participants received GSK1325756H 50 mg tablets via the oral route without food (fasted state) and 240 milliliters of water in Part 2.
Measure Participants	16	16
Temperature, 4 hours	0.06 (0.236)	0.21 (0.340)
Temperature 24 hours	0.04 (0.250)	0.10 (0.316)
Temperature, 48 hours	0.10 (0.228)	0.10 (0.312)

39. Primary Outcome

Title	Change From Baseline in Electrocardiogram (ECG) Parameters PR Interval, QRS Duration, Uncorrected QT Interval and Corrected QT Frederica's Correction) Interval
Description	Single 12-lead ECG's were obtained from Baseline and up to 72 hours in Part 1 using an ECG machine that automatically calculated the heart rate and measured PR Interval, QRS Duration, Uncorrected QT interval and Corrected QT (Fridericia's correction) interval. Baseline was defined as pre-dose assessments performed on Day 1. Change from Baseline was calculated by subtracting the post-dose-visit value from the Baseline value. Only those participants with data available at the specified time were analyzed (represented by n=x in the category titles).
Time Frame	Baseline and up to 72 hours in Part 1

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Part 1: Placebo (Fed)	Part 1: GSK1325756H 10 mg (Fed)	Part 1: GSK1325756H 50 mg (Fed)	Part 1: GSK1325756H 100 mg (Fed)
Arm/Group Description	Participants received matching placebo tablets via the oral route with food (fed state) and 240 milliliters of water in Part 1.	Participants received GSK1325756H 10 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 1.	Participants received GSK1325756H 50 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 1.	Participants received GSK1325756H 100 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 1.
Measure Participants	18	12	12	11
PR Interval, 4 hours	-0.9 (11.65)	0.7 (5.28)	1.3 (4.29)	0.5 (3.70)
PR Interval 24 hours	2.3 (5.63)	3.0 (7.56)	4.3 (6.20)	3.6 (5.57)
PR Interval, 48 hours	5.6 (9.22)	-0.8 (8.50)	5.7 (9.18)	5.8 (6.84)
PR Interval, 72 hours	6.7 (11.57)	6.0 (6.26)
QRS duration, 4 hours	-0.4 (2.12)	-0.3 (2.39)	-0.2 (1.59)	-0.2 (3.03)
QRS duration, 24 hours	0.4 (1.89)	0.7 (1.97)	0.7 (1.56)	0.4 (1.75)
QRS duration, 48 hours	1.0 (1.97)	2.8 (1.99)	1.7 (1.87)	0.5 (2.02)
QRS duration, 72 hours	1.7 (2.34)	0.9 (2.74)
Uncorrected QT Interval, 4 hours	-1.7 (10.98)	-4.2 (15.90)	-4.0 (10.23)	-2.9 (11.08)
Uncorrected QT Interval, 24 hours	-1.8 (10.74)	6.8 (15.69)	-1.0 (9.82)	-1.5 (11.70)
Uncorrected QT Interval, 48 hours	-4.4 (8.69)	-6.8 (12.52)	-1.5 (11.48)	-0.2 (14.76)
Uncorrected QT Interval, 72 hours	-8.3 (13.29)	-4.5 (14.54)
Corrected QT Interval, 4 hours	-9.7 (5.32)	-11.3 (5.14)	-10.8 (7.16)	-8.1 (5.36)
Corrected QT Interval, 24 hours	-7.6 (6.39)	-8.3 (7.75)	-9.5 (4.83)	-6.5 (6.02)
Corrected QT Interval, 48 hours	-8.7 (6.45)	-5.9 (7.44)	-10.7 (6.51)	-6.9 (9.59)
Corrected QT Interval,, 72 hours	-10.3 (3.27)	-7.6 (7.10)

40. Primary Outcome

Title	Change From Baseline in Electrocardiogram Parameters PR Interval, QRS Duration, Uncorrected QT Interval and Corrected QT (Frederica's Correction) Interval for Part 2
Description	Single 12-lead ECG's were obtained from Baseline and up to 72 hours in Part 2 using an ECG machine that automatically calculated the heart rate and measured PR Interval, QRS Duration, Uncorrected QT interval and Corrected QT (Frederica's correction) interval. Baseline was defined as pre-dose assessments performed on Day 1. Change from Baseline was calculated by subtracting the post-dose-visit value from the Baseline value.
Time Frame	Baseline and up to 48 hours in Part 2

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Part 2: GSK1325756H 50 mg (Fed)	Part 2: GSK1325756H 50 mg (Fasted)
Arm/Group Description	Participants received GSK1325756H 50 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 2.	Participants received GSK1325756H 50 mg tablets via the oral route without food (fasted state) and 240 milliliters of water in Part 2.
Measure Participants	16	16
PR Interval, 4 hours	-1.5 (5.59)	-0.6 (4.18)
PR Interval 24 hours	-2.5 (7.50)	1.3 (4.37)
PR Interval, 48 hours	1.5 (8.84)	4.1 (6.13)
QRS duration, 4 hours	-0.6 (2.28)	-1.3 (4.12)
QRS duration, 24 hours	-1.0 (2.19)	-1.8 (5.00)
QRS duration, 48 hours	-0.6 (2.50)	-0.9 (4.26)
Uncorrected QT Interval, 4 hours	3.1 (12.31)	6.4 (10.02)
Uncorrected QT Interval, 24 hours	-10.0 (15.85)	-3.9 (13.83)
Uncorrected QT Interval, 48 hours	-6.4 (11.25)	-9.5 (17.84)
Corrected QT Interval, 4 hours	-3.1 (6.55)	3.1 (7.20)
Corrected QT Interval, 24 hours	-6.1 (6.73)	-3.8 (7.38)
Corrected QT Interval, 48 hours	-5.7 (5.58)	-7.3 (8.69)

41. Primary Outcome

Title	Blood Concentration of GSK1325756 in Part 1
Description	Whole blood samples of approximately 1 milliliters were collected for measurement of blood concentrations of GSK1325756 at pre-dose and at 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours in all 3 periods; 60 and 72 hours post-dose in period-3 of part 1. Data has been presented for blood concentrations of GSK1325756 in fed state. Pharmacokinetic (PK) population was defined as participants who were administered at least one dose of study treatment and who had PK sample taken and analyzed. NA indicates standard deviation could not be calculated due to high proportion of non-quantifiable [NQ] values (more than 30% of values were imputed i.e., NQ assigned zero concentration) which affected the standard deviation and no sample was obtained per protocol for 60 and 72 hours.
Time Frame	Pre-dose and at 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours in all 3 periods; 60 and 72 hours post-dose in period-3 of Part 1

Outcome Measure Data

Analysis Population Description

PK Population

Arm/Group Title	Part 1: GSK1325756H 10 mg (Fed)	Part 1: GSK1325756H 50 mg (Fed)	Part 1: GSK1325756H 100 mg (Fed)
Arm/Group Description	Participants received GSK1325756H 10 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 1.	Participants received GSK1325756H 50 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 1.	Participants received GSK1325756H 100 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 1.
Measure Participants	12	12	11
Blood concentration, Pre-dose	0.000 (NA)	0.000 (NA)	0.000 (NA)
Blood concentration, 0.25 hours	1.425 (NA)	9.289 (NA)	32.318 (NA)
Blood concentration, 0.5 hours	24.350 (NA)	151.658 (196.5556)	201.782 (NA)
Blood concentration, 0.75 hours	59.951 (67.9706)	373.193 (376.8749)	426.032 (611.1420)
Blood concentration, 1 hour	94.150 (86.0423)	455.042 (350.7416)	634.955 (767.2316)
Blood concentration,, 2 hours	153.395 (100.0463)	971.417 (598.1981)	1285.524 (1017.193)
Blood concentration, 3 hours	154.733 (67.6734)	950.852 (443.1637)	1235.273 (740.0601)
Blood concentration, 4 hours	177.417 (47.6187)	966.658 (395.2375)	1498.000 (607.8816)
Blood concentration, 6 hours	126.817 (37.7057)	639.667 (251.0068)	1418.545 (497.2105)
Blood concentration, 8 hours	76.567 (25.8472)	386.667 (153.4840)	735.700 (234.1135)
Blood concentration, 10 hours	55.358 (16.1098)	295.250 (96.3848)	620.636 (217.5446)
Blood concentration,12 hours	39.742 (10.1591)	204.192 (70.3804)	411.091 (143.5280)
Blood concentration, 24 hours	16.363 (4.9104)	77.342 (37.3054)	160.982 (61.3081)
Blood concentration, 48 hours	3.423 (NA)	24.387 (13.2219)	43.282 (17.8091)
Blood concentration, 60 hours	NA (NA)	NA (NA)	19.087 (11.6452)
Blood concentration, 72 hours	NA (NA)	NA (NA)	18.403 (12.5176)

42. Primary Outcome

Title	Blood Concentration of GSK1325756 in Part 2
Description	Whole blood samples of approximately 1 milliliters were collected for measurement of blood concentrations of GSK1325756 at Pre-dose and at 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours post-dose in part 1. Data has been presented for blood concentrations of GSK1325756 in fasted and fed state. NA indicates standard deviation could not be calculated due to high proportion of NQ values (more than 30% of values were imputed i.e., NQ assigned zero concentration) which affected the standard deviation.
Time Frame	Pre-dose and at 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours post-dose in Part 2

Outcome Measure Data

Analysis Population Description

PK Population

Arm/Group Title	Part 2: GSK1325756H 50 mg (Fed)	Part 2: GSK1325756H 50 mg (Fasted)
Arm/Group Description	Participants received GSK1325756H 50 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 2.	Participants received GSK1325756H 50 mg tablets via the oral route without food (fasted state) and 240 milliliters of water in Part 2.
Measure Participants	16	16
Blood concentration, Pre-dose	0.000 (NA)	0.000 (NA)
Blood concentration, 0.25 hours	23.888 (NA)	434.557 (551.7663)
Blood concentration, 0.5 hours	248.749 (NA)	2233.813 (1476.075)
Blood concentration, 0.75 hours	363.644 (745.3481)	3599.500 (1240.578)
Blood concentration, 1 hour	470.700 (711.2266)	4210.625 (1361.315)
Blood concentration, 2 hours	1039.688 (638.7844)	3176.000 (691.7762)
Blood concentration, 3 hours	1499.250 (657.7378)	2156.250 (521.9307)
Blood concentration, 4 hours	1682.667 (478.1134)	1960.625 (402.0194)
Blood concentration, 6 hours	774.938 (305.5721)	640.500 (140.6840)
Blood concentration, 8 hours	463.750 (143.7101)	410.625 (105.4564)
Blood concentration, 10 hours	364.438 (117.3348)	350.813 (112.8440)
Blood concentration,12 hours	244.938 (76.6059)	254.188 (68.8847)
Blood concentration, 24 hours	111.163 (43.6251)	118.888 (53.3676)
Blood concentration, 48 hours	40.568 (61.6334)	29.918 (32.5396)

43. Primary Outcome

Title	Maximum Observed Concentration (Cmax) of GSK1325756H for Part 1
Description	Blood samples were collected at the indicated time points after administration of study treatment to investigate the PK profile of GSK1325756H in fasted state. PK parameters were calculated by standard non-compartmental analysis using Phoenix WinNonlin Version 6.4 or higher based on actual sampling times.
Time Frame	Pre-dose and at 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours in all 3 periods; 60 and 72 hours post-dose in period-3 of Part 1

Outcome Measure Data

Analysis Population Description

PK Population

Arm/Group Title	Part 1: GSK1325756H 10 mg (Fed)	Part 1:GSK1325756H 50 mg (Fed)	Part 1: GSK1325756H 100 mg (Fed)
Arm/Group Description	Participants received GSK1325756H 10 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 1.	Participants received GSK1325756H 50 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 1.	Participants received GSK1325756H 100 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 1.
Measure Participants	12	12	11
Geometric Mean (Geometric Coefficient of Variation) [Nanograms/milliliter]	217.082 (17.8)	1219.883 (37.3)	1924.864 (39.6)

44. Primary Outcome

Title	Area Under the Concentration-time Curve From Time 0 to t (AUC [0-t]) of GSK1325756H for Part 1
Description	Blood samples were collected at the indicated time points after administration of study treatment to investigate the PK profile of GSK1325756H in fasted state. PK parameters were calculated by standard non-compartmental analysis using Phoenix WinNonlin Version 6.4 or higher based on actual sampling times.
Time Frame	Pre-dose and at 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours in all 3 periods; 60 and 72 hours post-dose in period-3 of Part 1

Outcome Measure Data

Analysis Population Description

PK Population

Arm/Group Title	Part 1: GSK1325756H 10 mg (Fed)	Part 1: GSK1325756H 50 mg (Fed)	Part 1: GSK1325756H 100 mg (Fed)
Arm/Group Description	Participants received GSK1325756H 10 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 1.	Participants received GSK1325756H 50 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 1.	Participants received GSK1325756H 100 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 1.
Measure Participants	12	12	11
Geometric Mean (Geometric Coefficient of Variation) [Hours*nanograms/milliliter]	1622.2891 (21.7)	8872.6074 (30.2)	16681.8331 (25.2)

45. Primary Outcome

Title	Area Under the Concentration-time Curve From Time 0 to Infinity (AUC [0-inf]) of GSK1325756H for Part 1
Description	Blood samples were collected at the indicated time points after administration of study treatment to investigate the PK profile of GSK1325756H in fasted state. PK parameters were calculated by standard non-compartmental analysis using Phoenix WinNonlin Version 6.4 or higher based on actual sampling times.
Time Frame	Pre-dose and at 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours in all 3 periods; 60 and 72 hours post-dose in period-3 of Part 1

Outcome Measure Data

Analysis Population Description

PK Population

Arm/Group Title	Part 1: GSK1325756H 10 mg (Fed)	Part 1: GSK1325756H 50 mg (Fed)	Part 1: GSK1325756H 100 mg (Fed)
Arm/Group Description	Participants received GSK1325756H 10 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 1.	Participants received GSK1325756H 50 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 1.	Participants received GSK1325756H 100 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 1.
Measure Participants	12	12	11
Geometric Mean (Geometric Coefficient of Variation) [Hours*nanograms/milliliter]	1779.0163 (18.8)	9253.2108 (31.3)	17072.6642 (24.4)

46. Primary Outcome

Title	Area Under the Concentration-time Curve From Time 0 to 24 Hours (AUC [0-24]) of GSK1325756H for Part 1
Description	Blood samples were collected at the indicated time points after administration of study treatment to investigate the PK profile of GSK1325756H in fasted state. PK parameters were calculated by standard non-compartmental analysis using Phoenix WinNonlin Version 6.4 or higher based on actual sampling times.
Time Frame	Pre-dose and at 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours in all 3 periods; 60 and 72 hours post-dose in period-3 of Part 1

Outcome Measure Data

Analysis Population Description

PK Population

Arm/Group Title	Part 1: GSK1325756H 10 mg (Fed)	Part 1: GSK1325756H 50 mg (Fed)	Part 1: GSK1325756H 100 mg (Fed)
Arm/Group Description	Participants received GSK1325756H 10 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 1.	Participants received GSK1325756H 50 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 1.	Participants received GSK1325756H 100 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 1.
Measure Participants	12	12	11
Geometric Mean (Geometric Coefficient of Variation) [Hours*nanograms/milliliter]	1500.0109 (14.7)	7831.8861 (29.9)	14000.5473 (27.1)

47. Primary Outcome

Title	Time to Maximum Observed Concentration (Tmax) of GSK1325756H for Part 1
Description	Blood samples were collected at the indicated time points after administration of study treatment to investigate the PK profile of GSK1325756H in fasted state. PK parameters were calculated by standard non-compartmental analysis using Phoenix WinNonlin Version 6.4 or higher based on actual sampling times.
Time Frame	Pre-dose and at 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours in all 3 periods; 60 and 72 hours post-dose in period-3 of Part 1

Outcome Measure Data

Analysis Population Description

PK Population

Arm/Group Title	Part 1: GSK1325756H 10 mg (Fed)	Part 1: GSK1325756H 50 mg (Fed)	Part 1: GSK1325756H 100 mg (Fed)
Arm/Group Description	Participants received GSK1325756H 10 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 1.	Participants received GSK1325756H 50 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 1.	Participants received GSK1325756H 100 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 1.
Measure Participants	12	12	11
Median (Full Range) [Hours]	3.50000	3.00000	4.00000

48. Primary Outcome

Title	Terminal Half-life (t1/2) of GSK1325756H for Part 1
Description	Blood samples were collected at the indicated time points after administration of study treatment to investigate the PK profile of GSK1325756 in fasted state. PK parameters were calculated by standard non-compartmental analysis using Phoenix WinNonlin Version 6.4 or higher based on actual sampling times.
Time Frame	Pre-dose and at 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours in all 3 periods; 60 and 72 hours post-dose in period-3 of Part 1

Outcome Measure Data

Analysis Population Description

PK Population

Arm/Group Title	Part 1: GSK1325756H 10 mg (Fed)	Part 1: GSK1325756H 50 mg (Fed)	Part 1: GSK1325756H 100 mg (Fed)
Arm/Group Description	Participants received GSK1325756H 10 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 1.	Participants received GSK1325756H 50 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 1.	Participants received GSK1325756H 100 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 1.
Measure Participants	12	12	11
Mean (Standard Deviation) [Hours]	10.53043 (2.938579)	11.17318 (2.284423)	13.15755 (4.540486)

49. Primary Outcome

Title	Lag Time Before Observable Concentration (Tlag) of GSK1325756H for Part 1
Description	Blood samples were collected at the indicated time points after administration of study treatment to investigate the PK profile of GSK1325756 in fasted state. PK parameters were calculated by standard non-compartmental analysis using Phoenix WinNonlin Version 6.4 or higher based on actual sampling times.
Time Frame	Pre-dose and at 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours in all 3 periods; 60 and 72 hours post-dose in period-3 of Part 1

Outcome Measure Data

Analysis Population Description

PK Population

Arm/Group Title	Part 1: GSK1325756H 10 mg (Fed)	Part 1: GSK1325756H 50 mg (Fed)	Part 1: GSK1325756H 100 mg (Fed)
Arm/Group Description	Participants received GSK1325756H 10 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 1.	Participants received GSK1325756H 50 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 1.	Participants received GSK1325756H 100 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 1.
Measure Participants	12	12	11
Median (Full Range) [Hours]	0.37500	0.25000	0.25000

50. Primary Outcome

Title	Time to Last Quantifiable Concentration (Tlast) of the Blood Concentration of GSK1325756H for Part 1
Description	Blood samples were collected at the indicated time points after administration of study treatment to investigate the PK profile of GSK1325756H in fasted state. PK parameters were calculated by standard non-compartmental analysis using Phoenix WinNonlin Version 6.4 or higher based on actual sampling times.
Time Frame	Pre-dose and at 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours in all 3 periods; 60 and 72 hours post-dose in period-3 of Part 1

Outcome Measure Data

Analysis Population Description

PK Population

Arm/Group Title	Part 1: GSK1325756H 10 mg (Fed)	Part 1: GSK1325756H 50 mg (Fed)	Part 1: GSK1325756H 100 mg (Fed)
Arm/Group Description	Participants received GSK1325756H 10 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 1.	Participants received GSK1325756H 50 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 1.	Participants received GSK1325756H 100 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 1.
Measure Participants	12	12	11
Median (Full Range) [Hours]	36.00000	48.00000	72.00000

51. Primary Outcome

Title	Cmax of GSK1325756H for Part 2
Description	Blood samples were collected at the indicated time points after administration of study treatment to investigate the PK profile of GSK1325756H in fasted state. PK parameters were calculated by standard non-compartmental analysis using Phoenix WinNonlin Version 6.4 or higher based on actual sampling times.
Time Frame	Pre-dose and at 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours post-dose in Part 2

Outcome Measure Data

Analysis Population Description

PK Population

Arm/Group Title	Part 2: GSK1325756H 50 mg (Fed)	Part 2: GSK1325756H 50 mg (Fasted)
Arm/Group Description	Participants received GSK1325756H 50 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 2.	Participants received GSK1325756H 50 mg tablets via the oral route without food (fasted state) and 240 milliliters of water in Part 2.
Measure Participants	16	16
Geometric Mean (Geometric Coefficient of Variation) [Nanograms/milliliter]	1818.544 (32.5)	4146.886 (34.5)

52. Primary Outcome

Title	AUC (0-t) of GSK1325756H for Part 2
Description	Blood samples were collected at the indicated time points after administration of study treatment to investigate the PK profile of GSK1325756H in fasted state. PK parameters were calculated by standard non-compartmental analysis using Phoenix WinNonlin Version 6.4 or higher based on actual sampling times.
Time Frame	Pre-dose and at 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours post-dose in Part 2

Outcome Measure Data

Analysis Population Description

PK Population

Arm/Group Title	Part 2: GSK1325756H 50 mg (Fed)	Part 2: GSK1325756H 50 mg (Fasted)
Arm/Group Description	Participants received GSK1325756H 50 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 2.	Participants received GSK1325756H 50 mg tablets via the oral route without food (fasted state) and 240 milliliters of water in Part 2.
Measure Participants	16	16
Geometric Mean (Geometric Coefficient of Variation) [Hours*nanograms/milliliter]	11880.9038 (28.9)	18303.0441 (22.1)

53. Primary Outcome

Title	AUC (0-inf) of GSK1325756H for Part 2
Description	Blood samples were collected at the indicated time points after administration of study treatment to investigate the PK profile of GSK1325756H in fasted state. PK parameters were calculated by standard non-compartmental analysis using Phoenix WinNonlin Version 6.4 or higher based on actual sampling times. Only those participants with data available at the indicated time points were analyzed.
Time Frame	Pre-dose and at 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours post-dose in Part 2

Outcome Measure Data

Analysis Population Description

PK Population

Arm/Group Title	Part 2: GSK1325756H 50 mg (Fed)	Part 2: GSK1325756H 50 mg (Fasted)
Arm/Group Description	Participants received GSK1325756H 50 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 2.	Participants received GSK1325756H 50 mg tablets via the oral route without food (fasted state) and 240 milliliters of water in Part 2.
Measure Participants	15	16
Geometric Mean (Geometric Coefficient of Variation) [Hours*nanograms/milliliter]	12143.8862 (28.8)	18910.7975 (24.2)

54. Primary Outcome

Title	AUC (0-24) of GSK1325756H for Part 2
Description	Blood samples were collected at the indicated time points after administration of study treatment to investigate the PK profile of GSK1325756H in fasted state. PK parameters were calculated by standard non-compartmental analysis using Phoenix WinNonlin Version 6.4 or higher based on actual sampling times.
Time Frame	Pre-dose and at 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours post-dose in Part 2

Outcome Measure Data

Analysis Population Description

PK Population

Arm/Group Title	Part 2: GSK1325756H 50 mg (Fed)	Part 2: GSK1325756H 50 mg (Fasted)
Arm/Group Description	Participants received GSK1325756H 50 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 2.	Participants received GSK1325756H 50 mg tablets via the oral route without food (fasted state) and 240 milliliters of water in Part 2.
Measure Participants	16	16
Geometric Mean (Geometric Coefficient of Variation) [Hours*nanograms/milliliter]	10433.9293 (25.8)	16856.0664 (21.2)

55. Primary Outcome

Title	Tmax of GSK1325756H for Part 2
Description	Blood samples were collected at the indicated time points after administration of study treatment to investigate the PK profile of GSK1325756H in fasted state. PK parameters were calculated by standard non-compartmental analysis using Phoenix WinNonlin Version 6.4 or higher based on actual sampling times.
Time Frame	Pre-dose and at 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours post-dose in Part 2

Outcome Measure Data

Analysis Population Description

PK Population

Arm/Group Title	Part 2: GSK1325756H 50 mg (Fed)	Part 2: GSK1325756H 50 mg (Fasted)
Arm/Group Description	Participants received GSK1325756H 50 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 2.	Participants received GSK1325756H 50 mg tablets via the oral route without food (fasted state) and 240 milliliters of water in Part 2.
Measure Participants	16	16
Median (Full Range) [Hours]	3.00000	1.00000

56. Primary Outcome

Title	t1/2 of GSK1325756H for Part 2
Description	Blood samples were collected at the indicated time points after administration of study treatment to investigate the PK profile of GSK1325756H in fasted state. PK parameters were calculated by standard non-compartmental analysis using Phoenix WinNonlin Version 6.4 or higher based on actual sampling times. Only those participants with data available at the indicated time points were analyzed.
Time Frame	Pre-dose and at 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours post-dose in Part 2

Outcome Measure Data

Analysis Population Description

PK Population

Arm/Group Title	Part 2: GSK1325756H 50 mg (Fed)	Part 2: GSK1325756H 50 mg (Fasted)
Arm/Group Description	Participants received GSK1325756H 50 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 2.	Participants received GSK1325756H 50 mg tablets via the oral route without food (fasted state) and 240 milliliters of water in Part 2.
Measure Participants	15	16
Mean (Standard Deviation) [Hours]	10.75500 (2.928804)	11.09246 (5.259109)

57. Primary Outcome

Title	Tlag of GSK1325756H for Part 2
Description	Blood samples were collected at the indicated time points after administration of study treatment to investigate the PK profile of GSK1325756H in fasted state. PK parameters were calculated by standard non-compartmental analysis using Phoenix WinNonlin Version 6.4 or higher based on actual sampling times.
Time Frame	Pre-dose and at 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours post-dose in Part 2

Outcome Measure Data

Analysis Population Description

PK Population

Arm/Group Title	Part 2: GSK1325756H 50 mg (Fed)	Part 2: GSK1325756H 50 mg (Fasted)
Arm/Group Description	Participants received GSK1325756H 50 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 2.	Participants received GSK1325756H 50 mg tablets via the oral route without food (fasted state) and 240 milliliters of water in Part 2.
Measure Participants	16	16
Median (Full Range) [Hours]	0.25000	0.00000

58. Primary Outcome

Title	Tlast of the Blood Concentration of GSK1325756H for Part 2
Description	Blood samples were collected at the indicated time points after administration of study treatment to investigate the PK profile of GSK1325756H in fasted state. PK parameters were calculated by standard non-compartmental analysis using Phoenix WinNonlin Version 6.4 or higher based on actual sampling times.
Time Frame	Pre-dose and at 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48 post-dose in Part 2

Outcome Measure Data

Analysis Population Description

PK Population

Arm/Group Title	Part 2: GSK1325756H 50 mg (Fed)	Part 2: GSK1325756H 50 mg (Fasted)
Arm/Group Description	Participants received GSK1325756H 50 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 2.	Participants received GSK1325756H 50 mg tablets via the oral route without food (fasted state) and 240 milliliters of water in Part 2.
Measure Participants	16	16
Median (Full Range) [Hours]	48.00000	48.00000

Adverse Events

Time Frame	AEs and SAEs were collected from the Day -1 up to follow-up ( 32 days for Part 1 and up to 21 days for Part 2)
Adverse Event Reporting Description	Safety Population was used for analysis of AE and SAE's.
Arm/Group Title	Part 1: Placebo (Fed)		Part 1: GSK1325756H 10 mg (Fed)		Part 1: GSK1325756H 50 mg (Fed)		Part 1: GSK1325756H 100 mg (Fed)		Part 2: GSK1325756H 50 mg (Fed)		Part 2: GSK1325756H 50 mg (Fasted)
Arm/Group Description	Participants received matching placebo tablets via the oral route with food (fed state) and 240 milliliters of water in Part 1.		Participants received GSK1325756H 10 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 1.		Participants received GSK1325756H 50 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 1.		Participants received GSK1325756H 100 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 1.		Participants received GSK1325756H 50 mg tablets via the oral route with food (fed state) and 240 milliliters of water in Part 2.		Participants received GSK1325756H 50 mg tablets via the oral route without food (fasted state) and 240 mililiters of water in Part 2.
All Cause Mortality
	Part 1: Placebo (Fed)		Part 1: GSK1325756H 10 mg (Fed)		Part 1: GSK1325756H 50 mg (Fed)		Part 1: GSK1325756H 100 mg (Fed)		Part 2: GSK1325756H 50 mg (Fed)		Part 2: GSK1325756H 50 mg (Fasted)
	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	0/18 (0%)		0/12 (0%)		0/12 (0%)		0/11 (0%)		0/16 (0%)		0/16 (0%)
Serious Adverse Events
	Part 1: Placebo (Fed)		Part 1: GSK1325756H 10 mg (Fed)		Part 1: GSK1325756H 50 mg (Fed)		Part 1: GSK1325756H 100 mg (Fed)		Part 2: GSK1325756H 50 mg (Fed)		Part 2: GSK1325756H 50 mg (Fasted)
	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	0/18 (0%)		0/12 (0%)		0/12 (0%)		0/11 (0%)		0/16 (0%)		0/16 (0%)
Other (Not Including Serious) Adverse Events
	Part 1: Placebo (Fed)		Part 1: GSK1325756H 10 mg (Fed)		Part 1: GSK1325756H 50 mg (Fed)		Part 1: GSK1325756H 100 mg (Fed)		Part 2: GSK1325756H 50 mg (Fed)		Part 2: GSK1325756H 50 mg (Fasted)
	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	1/18 (5.6%)		0/12 (0%)		0/12 (0%)		1/11 (9.1%)		1/16 (6.3%)		0/16 (0%)
Infections and infestations
Herpes zoster	0/18 (0%)		0/12 (0%)		0/12 (0%)		1/11 (9.1%)		0/16 (0%)		0/16 (0%)
Viral upper respiratory tract infection	1/18 (5.6%)		0/12 (0%)		0/12 (0%)		0/11 (0%)		0/16 (0%)		0/16 (0%)
Investigations
Blood uric acid increased	0/18 (0%)		0/12 (0%)		0/12 (0%)		0/11 (0%)		1/16 (6.3%)		0/16 (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.