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Trial record 43 of 948 for:    tablet | Japan

Daprodustat Bioequivalence and Food Effect Study

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03493386
Recruitment Status : Completed
First Posted : April 10, 2018
Results First Posted : August 6, 2019
Last Update Posted : August 6, 2019
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Brief Summary:
This is two-way crossover study to compare pharmacokinetic (PK) of daprodustat 2 milligram (mg) versus 4 mg tablets and food effect on the PK of daprodustat following single oral doses in healthy Japanese male subjects. This study will be conducted in two parts. Part 1 is the bioequivalence part in which subjects will receive single dose of 2 tablets of 2 mg daprodustat and single dose of 1 tablet of 4 mg daprodustat in crossover manner. Part 2 is Food effect part. In this part, subjects will receive single dose of 4 mg daprodustat tablet in fasting and fed state in a crossover manner. There will 5-day wash-out period between each intervention period. There will be approximately 52 subjects in Part 1 and 12 subjects in Part 2. The study will last for 6 weeks.

Condition or disease Intervention/treatment Phase
Anaemia Drug: Daprodustat 2 mg tablet Drug: Daprodustat 4 mg tablet Phase 1

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 64 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description: This study will be conducted in two parts. Part 1 is the bioequivalence part in which subjects will receive single dose of 2 tablets of 2 mg daprodustat and single dose of 1 tablet of 4 mg daprodustat in crossover manner. Part 2 is Food effect part. In this part, subjects will receive single dose of 4 mg daprodustat tablet in fasting and fed state in a crossover manner.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Single Centre, Single Dose, Open-label, Randomised, 2-way Crossover Study in Healthy Japanese Male Subjects to Evaluate the Bioequivalence of Daprodustat Tablets (2 mg Tablet vs. 4 mg Tablet) (Part 1) and the Food Effect on the Pharmacokinetics of Daprodustat (Part 2)
Actual Study Start Date : April 24, 2018
Actual Primary Completion Date : June 9, 2018
Actual Study Completion Date : June 9, 2018

Arm Intervention/treatment
Experimental: Treatment Group A: Part 1
Subjects will be randomized to receive single dose of two tablets of 2 mg daprodustat in Period 1 and in Period 2 subjects will receive single dose of 4 mg daprodustat. There will be a wash-out period of 5 days between the Periods.
Drug: Daprodustat 2 mg tablet
Daprodustat is available as 2 mg tablet. Subjects will receive daprodustat orally as tablet. A single dose of 2 tablets of 2 mg daprodustat will be administered in a fasted state during Part 1 of the study.

Drug: Daprodustat 4 mg tablet
Daprodustat is available as 4 mg tablet. Subjects will receive daprodustat orally as tablet. A single dose of 4 mg daprodustat will be administered in a fasted state during Part 1 and in fed and fasted state in Part 2 of the study.

Experimental: Treatment Group B: Part 1
Subjects will be randomized to receive single dose of 4 mg daprodustat in Period 1 and in Period 2 subjects will receive single dose of two tablets of 2 mg daprodustat. There will be a wash-out period of 5 days between the Periods.
Drug: Daprodustat 2 mg tablet
Daprodustat is available as 2 mg tablet. Subjects will receive daprodustat orally as tablet. A single dose of 2 tablets of 2 mg daprodustat will be administered in a fasted state during Part 1 of the study.

Drug: Daprodustat 4 mg tablet
Daprodustat is available as 4 mg tablet. Subjects will receive daprodustat orally as tablet. A single dose of 4 mg daprodustat will be administered in a fasted state during Part 1 and in fed and fasted state in Part 2 of the study.

Experimental: Treatment Group C: Part 2
Subjects will be randomized to receive single dose of 4 mg daprodustat in fed state during Period 1 and in Period 2 subjects will receive single dose of 4 mg daprodustat in fasted state. There will be a wash-out period of 5 days between the Periods.
Drug: Daprodustat 4 mg tablet
Daprodustat is available as 4 mg tablet. Subjects will receive daprodustat orally as tablet. A single dose of 4 mg daprodustat will be administered in a fasted state during Part 1 and in fed and fasted state in Part 2 of the study.

Experimental: Treatment Group D: Part 2
Subjects will be randomized to receive single dose of 4 mg daprodustat in fasted state during period 1 and in Period 2 subjects will receive single dose of 4 mg daprodustat in fed state. There will be a wash-out period of 5 days between the Periods.
Drug: Daprodustat 4 mg tablet
Daprodustat is available as 4 mg tablet. Subjects will receive daprodustat orally as tablet. A single dose of 4 mg daprodustat will be administered in a fasted state during Part 1 and in fed and fasted state in Part 2 of the study.




Primary Outcome Measures :
  1. Part 1:Area Under Plasma Concentration-time Curve (AUC) From Zero Hours to Last Measurable Concentration (AUC[0-t]) and AUC From Zero Hours Extrapolated to Infinity AUC [0-inf] of Daprodustat [ Time Frame: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8 and 12 hours post-dose on Day 1, 24 hours post-dose on Day 2 ]
    Blood samples were collected at indicated timepoints and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin version 6.3. PK population comprised of all participants in the Safety population (all randomized participants) who received at least one dose of study intervention) who had at least 1 non-missing PK assessment.

  2. Part 1:Maximum Observed Drug Concentration (Cmax) of Daprodustat [ Time Frame: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8 and 12 hours post-dose on Day 1, 24 hours post-dose on Day 2 ]
    Blood samples were collected at indicated timepoints and pharmacokinetic (PK) analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin version 6.3.

  3. Part 1:Terminal Phase Half-life (T1/2) of Daprodustat and Mean Residence Time (MRT) [ Time Frame: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8 and 12 hours post-dose on Day 1, 24 hours post-dose on Day 2 ]
    Blood samples were collected at indicated timepoints and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin version 6.3.

  4. Part 1: Time of Occurrence of Cmax (Tmax) of Daprodustat [ Time Frame: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8 and 12 hours post-dose on Day 1, 24 hours post-dose on Day 2 ]
    Blood samples were collected at indicated timepoints and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin version 6.3.

  5. Part 1: Percentage of AUC (0-inf) Obtained by Extrapolation (Percentage AUCex) [ Time Frame: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8 and 12 hours post-dose on Day 1, 24 hours post-dose on Day 2 ]
    Blood samples were collected at indicated timepoints and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin version 6.3.

  6. Part 1:Apparent Clearance (CL/F) of Daprodustat [ Time Frame: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8 and 12 hours post-dose on Day 1, 24 hours post-dose on Day 2 ]
    Blood samples were collected at indicated timepoints and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin version 6.3.

  7. Part 1:Apparent Oral Volume of Distribution (Vz/F) of Daprodustat [ Time Frame: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8 and 12 hours post-dose on Day 1, 24 hours post-dose on Day 2 ]
    Blood samples were collected at indicated timepoints and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin version 6.3.

  8. Part 1: Elimination Rate Constant (Kel) of Daprodustat [ Time Frame: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8 and 12hours post-dose on Day 1, 24hours post-dose on Day 2 ]
    Blood samples were collected at indicated timepoints and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin version 6.3.

  9. Part 2:AUC[0-t] andAUC [0-inf] of Daprodustat [ Time Frame: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8 and 12hours post-dose on Day 1, 24hours post-dose on Day 2 ]
    Blood samples were collected at indicated timepoints and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin version 6.3.

  10. Part 2: Cmax of Daprodustat [ Time Frame: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8 and 12hours post-dose on Day 1, 24hours post-dose on Day 2 ]
    Blood samples were collected at indicated timepoints and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin version 6.3.

  11. Part 2: T1/2 and MRT of Daprodustat [ Time Frame: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8 and 12hours post-dose on Day 1, 24hours post-dose on Day 2 ]
    Blood samples were collected at indicated time points and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin version 6.3.

  12. Part 2: Tmax of Daprodustat [ Time Frame: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8 and 12 hours post-dose on Day 1, 24 hours post-dose on Day 2 ]
    Blood samples were collected at indicated timepoints and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin version 6.3.

  13. Part 2: Percentage AUCex of Dapordustat [ Time Frame: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8 and 12 hours post-dose on Day 1, 24 hours post-dose on Day 2 ]
    Blood samples were collected at indicated timepoints and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin version 6.3.

  14. Part 2: CL/F of Daprodustat [ Time Frame: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8 and 12 hours post-dose on Day 1, 24 hours post-dose on Day 2 ]
    Blood samples were collected at indicated timepoints and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin version 6.3.

  15. Part 2: Vz/F of Daprodustat [ Time Frame: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8 and 12 hours post-dose on Day 1, 24 hours post-dose on Day 2 ]
    Blood samples were collected at indicated timepoints and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin version 6.3.

  16. Part 2: Kel of Daprodustat [ Time Frame: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8 and 12 hours post-dose on Day 1, 24 hours post-dose on Day 2 ]
    Blood samples were collected at indicated timepoints and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin version 6.3.


Secondary Outcome Measures :
  1. Part 1: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Up to Day 16 ]
    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 randomized participants who took at least one dose of study treatment.

  2. Part 1: Change From Baseline Chemistry Paramters: Glucose, Calcium, Cholesterol, Chloride, High Density Lipoprotein (HDL) Cholesterol, Low Density Lipoprotein (LDL) Cholesterol, Potassium, Phosphate, Sodium, Triglycerides, and Urea. [ Time Frame: Baseline (Day -1), 24hours post-dose ]
    Blood samples were collected to analyze the chemistry parameters; glucose, calcium, cholesterol, chloride, HDL cholesterol, LDL cholesterol, potassium, phosphate, sodium, triglycerides, and urea. Day-1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the Post-Dose visit value.

  3. Part 1: Change From Baseline in Chemistry Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatine Kinase, Lactate Dehydrogenase and Gamma Glutamyl Transferase (GGT). [ Time Frame: Baseline (Day -1), 24hours post-dose ]
    Blood samples were collected to analyze the chemistry parameters; ALP, ALT, AST, creatine kinase, lactate dehydrogenase and GGT. Day-1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the Post-Dose visit value.

  4. Part 1: Change From Baseline in Chemistry Parameters; Albumin, Protein. [ Time Frame: Baseline (Day -1), 24hours post-dose ]
    Blood samples were collected to analyze the chemistry parameters; albumin, protein. Day-1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the Post-Dose visit value.

  5. Part 1: Change From Baseline in Chemistry Parameters; Direct Bilirubin, Bilirubin, Creatinine, Urate [ Time Frame: Baseline (Day -1), 24hours post-dose ]
    Blood samples were collected to analyze the chemistry parameters; direct bilirubin, bilirubin, creatinine, urate. Day-1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the Post-Dose visit value.

  6. Part 1:Change From Baseline in Hematology Parameter; Hematocrit [ Time Frame: Baseline (Day -1), 24hours post-dose ]
    Blood samples were collected to analyze hematology parameters; hematocrit, reticulocytes. Platelets. Day-1 (one day before the Pre-Dose) was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the Post-Dose visit value.

  7. Part 1:Change From Baseline in Hematology Parameter; Reticulocytes [ Time Frame: Baseline (Day -1), 24hours post-dose ]
    Blood samples were collected to analyze hematology parameters; reticulocytes. Day-1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the Post-Dose visit value.

  8. Part 1: Change From Baseline in Hematology Parameters; Hemoglobin (Hb), Erythrocyte Mean Corpuscular Hb Concentration (MCHC) [ Time Frame: Baseline (Day -1), 24hours post-dose ]
    Blood samples were collected to analyze hematology parameters; Hb, EMCH concentration. Day-1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the Post-Dose visit value.

  9. Part 1: Change From Baseline in Hematology Parameters; Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils [ Time Frame: Baseline (Day -1), 24hours post-dose ]
    Blood samples were collected to analyze hematology parameters; basophils, eosinophils, lymphocytes, monocytes, neutrophil. Day-1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the Post-Dose visit value.

  10. Part 1: Change From Baseline in Hematology Parameter Erythrocyte MCHC [ Time Frame: Baseline (Day -1), 24hours post-dose ]
    Blood samples were collected to analyze hematology parameter; EMCH. Day-1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the Post-Dose visit value.

  11. Part 1: Change From Baseline in Hematology Parameter Erythrocyte Mean Corpuscular Volume (EMCV) [ Time Frame: Baseline (Day -1), 24hours post-dose ]
    Blood samples were collected to analyze hematology parameter; EMCV. Day-1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the Post-Dose visit value.

  12. Part 1: Change From Baseline in Hematology Parameters Platelets, Leukocytes [ Time Frame: Baseline (Day -1), 24hours post-dose ]
    Blood samples were collected to analyze hematology parameter; platelets, leukocytes. Day-1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the Post-Dose visit value.

  13. Part 1: Change From Baseline in Hematology Parameter: Erythrocytes [ Time Frame: Baseline (Day -1), 24hours post-dose ]
    Blood samples were collected to analyze hematology parameter; erythrocytes. Day-1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the Post-Dose visit value.

  14. Part 1: Change From Baseline in Urinalysis Parameter; Potential of Hydrogen (pH) [ Time Frame: Baseline (Day -1), 24hours post-dose ]
    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 24 hours in Part 1.Day-1 (one day before the Pre-Dose) was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the Post-Dose visit value.

  15. Part 1: Change From Baseline in Urinalysis Parameter; Specific Gravity [ Time Frame: Baseline (Day -1), 24hours post-dose ]
    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 24 hours in Part 1. Day-1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the Post-Dose visit value.

  16. Part 1: Change From Baseline in Vital Signs; Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) [ Time Frame: Baseline (Day -1), 3 and 24 hours (post-dose) ]
    DBP and SBP were measured in semi-supine position after 5 minutes rest for the participants at indicated time points. Day 1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.

  17. Part 1: Change From Baseline in Pulse Rate [ Time Frame: Baseline (Day -1), 3 and 24 hours (post-dose) ]
    Pulse rate was measured in semi-supine position after 5 minutes rest for the participants at indicated time points. Day 1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.

  18. Part 1: Change From Baseline in Temperature [ Time Frame: Baseline (Day -1), 3 and 24 hours (post-dose) ]
    Temperature was measured in semi-supine position after 5 minutes rest for the participants at indicated time points. Day 1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.

  19. Part 1: Change From Baseline in Electrocardiogram (ECG) Parameter; Mean Heart Rate (HR) [ Time Frame: Baseline (Day -1), 3 and 24 hours (post-dose) ]
    Single 12-lead ECG's were obtained from 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 at given time point. Day -1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.

  20. Part 1: Change From Baseline in ECG Parameter; PR Interval, QRS Interval, QT Interval, QT Duration Corrected for Heart Rate by Friderician Formula (QTcF) Interval [ Time Frame: Baseline (Day -1), 3 and 24 hours (post-dose) ]
    Single 12-lead ECG's were obtained from 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 at given time point. Day -1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.

  21. Part 2: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Up to Day 16 ]
    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 randomized participants who took at least one dose of study treatment.

  22. Part 2: Change From Baseline Chemistry Parameters; Glucose, Calcium, Cholesterol, Chloride, HDL Cholesterol, LDL Cholesterol, Potassium, Phosphate, Sodium, Triglycerides, and Urea [ Time Frame: Baseline (Day -1), 24 hours (post-dose) ]
    Blood samples were collected to analyze the chemistry parameters; glucose, calcium, cholesterol, chloride, HDL cholesterol, LDL cholesterol, potassium, phosphate,sodium, triglycerides, and urea. Day-1 (one day before the Pre-Dose) was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the Post-Dose visit value.

  23. Part 2: Change From Baseline in Chemistry Paremeters; ALP, ALT, AST, Creatine Kinase, Lactate Dehydrogenase, GGT [ Time Frame: Baseline (Day -1), 24 hours (post-dose) ]
    Blood samples were collected to analyze the chemistry parameters; ALP,ALT, AST, creatine kinase, lactate dehydrogenase and GGT. Day-1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the Post-Dose visit value.

  24. Part 2: Change From Baseline in Chemistry Parameters; Albumin, Protein [ Time Frame: Baseline (Day -1), 24 hours (post-dose) ]
    Blood samples were collected to analyze the chemistry parameters; albumin, protein. Day-1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the Post-Dose visit value.

  25. Part 2: Change From Baseline in Chemistry Parameters; Direct Bilirubin, Bilirubin, Creatinine, Urate [ Time Frame: Baseline (Day -1), 24 hours (post-dose) ]
    Blood samples were collected to analyze the chemistry parameters; direct bilirubin, bilirubin, creatinine, urate. Day-1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the Post-Dose visit value.

  26. Part 2: Change From Baseline in Hematology Parameters; Hematocrit [ Time Frame: Baseline (Day -1), 24 hours (post-dose) ]
    Blood samples were collected to analyze hematology parameter; hematocrit. Day-1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the Post-Dose visit value.

  27. Part 2: Change From Baseline in Hematology Parameters; Reticulocytes [ Time Frame: Baseline (Day -1), 24 hours (post-dose) ]
    Blood samples were collected to analyze hematology parameter; reticulocytes. Day-1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the Post-Dose visit value.

  28. Part 2: Change From Baseline in Hematology Parameters; Hb, Erythrocyte MCHC [ Time Frame: Baseline (Day -1), 24 hours (post-dose) ]
    Blood samples were collected to analyze hematology parameters; Hb, erythrocyte MCHC. Day-1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the Post-Dose visit value.

  29. Part 2: Change From Baseline in Hematology Parameters; Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils [ Time Frame: Baseline (Day -1), 24 hours (post-dose) ]
    Blood samples were collected to analyze hematology parameters; basophils, eosinophils, lymphocytes, monocytes, neutrophils. Day-1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the Post-Dose visit value.

  30. Part 2: Change From Baseline in Hematology Parameter: EMCH [ Time Frame: Baseline (Day -1), 24 hours (post-dose) ]
    Blood samples were collected to analyze hematology parameter; EMCH. Day-1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the Post-Dose visit value.

  31. Part 2: Change From Baseline in Hematology Parameter EMCV [ Time Frame: Baseline (Day -1), 24 hours (post-dose) ]
    Blood samples were collected to analyze hematology parameter; EMCV. Day-1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the Post-Dose visit value.

  32. Part 2: Change From Baseline in Hematology Parameters Platelets, Leukocytes [ Time Frame: Baseline (Day -1), 24 hours (post-dose) ]
    Blood samples were collected to analyze hematology parameter; platelets, leukocytes. Day-1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the Post-Dose visit value.

  33. Part 2: Change From Baseline in Hematology Parameter Erythrocytes [ Time Frame: Baseline (Day -1), 24 hours (post-dose) ]
    Blood samples were collected to analyze hematology parameter; erythrocytes. Day-1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the Post-Dose visit value.

  34. Part 2: Change From Baseline in Urinalysis Parameter; Potential of Hydrogen (pH) [ Time Frame: Baseline (Day -1), 24 hours (post-dose) ]
    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 24 hours in Part 2. Day-1 (one day before the Pre-Dose) was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the Post-Dose visit value.

  35. Part 2: Change From Baseline in Urinalysis Parameter; Specific Gravity [ Time Frame: Baseline (Day -1), 24 hours (post-dose) ]
    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 24 hours in Part 2. Day-1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the Post-Dose visit value.

  36. Part 2: Change From Baseline in Vital Signs; Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) [ Time Frame: Baseline (Day -1),3 and 24hours (pre-dose) ]
    DBP and SBP were measured in semi-supine position after 5 minutes rest for the participants at indicated time point. Day-1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.

  37. Part 2: Change From Baseline in Pulse Rate [ Time Frame: Baseline (Day -1),3 and 24hours (pre-dose) ]
    Pulse rate was measured in semi-supine position after 5 minutes rest for the participants at indicated time points. Day -1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.

  38. Part 2: Change From Baseline in Temperature [ Time Frame: Baseline (Day -1),3 and 24hours (pre-dose) ]
    Temperature was measured in semi-supine position after 5 minutes rest for the participants at indicated time points. Day-1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.

  39. Part 2: Change From Baseline in ECG Parameter; Mean Heart Rate (HR) [ Time Frame: Baseline (Day -1),3 and 24hours (pre-dose) ]
    Single 12-lead ECG's were obtained from 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 at given time point. Day -1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.

  40. Part 2: Change From Baseline in ECG Parameter; PR Interval, QRS Interval, QT Interval, QTcF Interval [ Time Frame: Baseline (Day -1),3 and 24hours (pre-dose) ]
    Single 12-lead ECG's were obtained from 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 at given time point. Day -1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   20 Years to 55 Years   (Adult)
Sexes Eligible for Study:   Male
Gender Based Eligibility:   Yes
Gender Eligibility Description:   Japanese male subjects who will be overtly healthy as determined by medical evaluation will be included in the study.
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Subject must be 20 to 55 years of age inclusive, at the time of signing the informed consent.
  • Japanese subjects who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring.
  • Body weight > = 50 kilogram (kg) and body mass index (BMI) within the range 18.5 - 24.9 kilogram per meter square (kg/m^2).
  • Male subjects.
  • Subjects capable of giving signed informed consent.

Exclusion Criteria:

  • History or presence of cardiovascular(CV), respiratory, hepatic, renal, gastrointestinal (GI), endocrine, haematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study intervention; or interfering with the interpretation of data.
  • Abnormal blood pressure as determined by the investigator.
  • ALT >1.5x upper limit of normal (ULN).
  • Bilirubin >1.5xULN
  • Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
  • QTcF > 500 millisecond (msec). The QTcF is the QT interval corrected for heart rate according to Fridericia's formula, machine-read or manually over-read. The specific formula that will be used to determine eligibility and discontinuation for an individual subject should be determined prior to initiation of the study. In other words, several different formulae cannot be used to calculate the QT correction (QTc) for an individual subject and then the lowest QTc value used to include or discontinue the subject from the trial.
  • The values of Hgb at screening: >=16.0 gram per deciliter (g/dL).
  • History of deep vein thrombosis, pulmonary embolism or other thrombosis related condition.
  • History of myocardial infarction (MI) or acute coronary syndrome, stroke or transient ischemic attack.
  • Subjects that have undergone cholecystectomy.
  • History of malignancy within the prior 2 years or currently receiving treatment for cancer.
  • Any evidence of heart failure, as defined by the New York Heart Association (NYHA) functional classification system.
  • Past or intended use of over-the-counter or prescription medication including vitamins, diet foods and herbal medications within 14 days prior to first dosing.
  • Exposure to more than 4 new chemical entities within 12 months prior to the first dosing day.
  • Current enrolment or past participation (that is administration of last dose of investigational study intervention) within the last 30 days (or 5 half-lives, whichever is longer) before signing of consent in this clinical study involving an investigational study intervention or any other type of medical research.
  • The subject with positive serological test for syphilis (Rapid Plasma Reagin [RPR] and Treponema pallidum haemagglutination 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:for an average weekly intake of >14 units for males. One unit is equivalent to 350 milliliter (mL) of beer, 150 mL of wine or 45 mL of 80 proof distilled spirits.
  • Smoking or history of regular use of tobacco- or nicotine-containing products (example nicotine patch, electronic cigarette) within 6 months prior to screening.
  • Sensitivity to any of the study interventions, or components thereof, or drug or other allergy that, in the opinion of the investigator or medical monitor, contraindicates participation in the study.
  • History of donation of blood or blood products >= 400 mL within 3 months or >= 200 mL within 1 month prior to the first dosing day.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03493386


Locations
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Japan
GSK Investigational Site
Fukuoka, Japan, 813-0017
Sponsors and Collaborators
GlaxoSmithKline
Investigators
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Study Director: GSK Clinical Trials GlaxoSmithKline
  Study Documents (Full-Text)

Documents provided by GlaxoSmithKline:
Study Protocol  [PDF] March 12, 2018
Statistical Analysis Plan  [PDF] July 10, 2018


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Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT03493386     History of Changes
Other Study ID Numbers: 207727
First Posted: April 10, 2018    Key Record Dates
Results First Posted: August 6, 2019
Last Update Posted: August 6, 2019
Last Verified: May 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints of the study.
Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted when justified, for up to another 12 months.
URL: http://clinicalstudydatarequest.com

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by GlaxoSmithKline:
Japan
Crossover
Daprodustat
Bioequivalence
Pharmacokinetics
Additional relevant MeSH terms:
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Glycine
Glycine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs