Study of Danirixin in Japanese Healthy Elderly Male Subjects

Phase 1

Completed

• Conditions: Pulmonary Disease, Chronic Obstructive
• Interventions: Drug: GSK1325756H; Drug: Placebo

• Registration Number: NCT03136380
• Lead Sponsor: GlaxoSmithKline

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2017-04-17
• Study First Submitted QC: 2017-04-27
• Study First Posted: 2017-05-02
• Study Start: 2017-05-10
• Primary Completion: 2017-07-31
• Study Completion: 2017-07-31
• Results First Submitted: 2018-06-01
• Status Verified: 2019-01
• Results First Submitted QC: 2019-01-14
• Last Update Submitted: 2019-01-14
• Results First Posted: 2019-04-18
• Last Update Posted: 2019-04-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 34

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Part 1: Group A	GSK1325756H	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.
Part 1: Group B	Placebo	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.
Part 1: Group A	Placebo	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.
Part 1: Group B	GSK1325756H	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.
Part 1: Group C	GSK1325756H	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.
Part 2: Group E	GSK1325756H	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.
Part 1: Group C	Placebo	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.
Part 2: Group D	GSK1325756H	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.

Primary Outcome Measures

Name	Time	Method
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.
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
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).
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.
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).
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).
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).
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.
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).
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.
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.
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.
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).
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.
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).
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).
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).
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).
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.
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.
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.
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.
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.
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).
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.
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.
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).
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).
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.
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.
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.
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.
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).
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.
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.
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.
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.
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.
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.
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.
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.
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).
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.
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.
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.
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).
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.
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).
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.

Trial Locations

Locations (1)

GSK Investigational Site; 🇯🇵 Tokyo, Japan