Study of Danirixin in Japanese Healthy Elderly Male Subjects

• ClinicalTrials.gov Identifier: NCT03136380
• Recruitment Status: Completed
• First Posted: May 2, 2017
• Results First Posted: April 18, 2019
• Last Update Posted: April 18, 2019
• Sponsor: GlaxoSmithKline
• Information provided by (Responsible Party): GlaxoSmithKline

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 (Clinical Trial)
• 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: July 31, 2017
• Actual Study Completion Date: July 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ 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 ]
    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 [ 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 ]
    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 [ 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 ]
    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 [ 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 ]
    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 [ 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 ]
    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 [ 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 ]
    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 [ 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 ]
    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 [ 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 ]
    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 [ 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 ]
    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 [ 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 ]
    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 [ 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 ]
    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 [ 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 ]
    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 [ 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 ]
    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 [ 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 ]
    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 [ 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 ]
    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 [ 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 ]
    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 [ 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 ]
    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 [ 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 ]
    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

• Ages Eligible for Study: 65 Years and older (Older Adult)
• Sexes Eligible for Study: Male
• Gender Based Eligibility: Yes
• Gender Eligibility Description: Japanese Healthy Elderly Male Subjects
• Accepts Healthy Volunteers: Yes

Criteria

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

Japan

GSK Investigational Site

Tokyo, Japan, 162-0053

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)

Documents provided by GlaxoSmithKline:

Study Protocol  [PDF] May 8, 2017

Statistical Analysis Plan  [PDF] July 11, 2017

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Iida T, Matsuzawa Y, Ogura H, Nagakubo T, Wakamatsu A, Ambery C, Miller BE, Lazaar AL, Numachi Y. Evaluation of the Safety, Tolerability, Pharmacokinetics, and Food Effect of Danirixin Hydrobromide Tablets in Japanese Healthy Elderly Participants. Clin Pharmacol Drug Dev. 2019 Nov;8(8):1081-1087. doi: 10.1002/cpdd.693. Epub 2019 May 6.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT03136380
• Other Study ID Numbers: 206817
• First Posted: May 2, 2017
• Results First Posted: April 18, 2019
• Last Update Posted: April 18, 2019
• Last Verified: January 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; Lung Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive