Daprodustat Bioequivalence and Food Effect Study

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03493386
• Collaborator: (none)
• Enrollment: 64
• Location: 1
• Arms: 4
• Actual Duration (Months): 1.5
• Patients Per Site Per Month: 42.3

Study Details

Study Description

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

Study Design

• Study Type: Interventional
• 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.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: Apr 24, 2018
• Actual Primary Completion Date: Jun 9, 2018
• Actual Study Completion Date: Jun 9, 2018

Arms and Interventions

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.

Outcome Measures

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 [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 [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) [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 [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) [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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) [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. [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). [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. [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 [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 [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 [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) [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 [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 [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) [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 [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 [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) [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 [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) [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 [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 [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) [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 [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) [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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) [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 [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) [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 [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 [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) [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 [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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years to 55 Years
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: Yes

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Fukuoka		Japan	813-0017

Sponsors and Collaborators

• GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

• Study Protocol - Mar 12, 2018
• Statistical Analysis Plan - Jul 10, 2018

More Information

Publications

• Yamada M, Osamura M, Ogura H, Onoue T, Wakamatsu A, Numachi Y, Caltabiano S, Mahar KM. A Single-Dose, Open-Label, Randomized, Two-Way Crossover Study in Healthy Japanese Participants to Evaluate the Bioequivalence and the Food Effect on the Pharmacokinetics of Daprodustat. Clin Pharmacol Drug Dev. 2020 Nov;9(8):978-984. doi: 10.1002/cpdd.793. Epub 2020 Apr 6.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT03493386
• Other Study ID Numbers: 207727
• First Posted: Apr 10, 2018
• Last Update Posted: Jul 8, 2020
• Last Verified: Jun 1, 2020

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• 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: Glycine

Study Results

Participant Flow

Recruitment Details	A single center, single dose, open-label, randomized, 2-way crossover study in healthy Japanese male participants to evaluate the bioequivalence of daprodustat tablets, study was conducted at one center in Japan.
Pre-assignment Detail	Total 64 healthy participants were enrolled in the study which was conducted from 24-April-18 to 09-June-18, study was conducted in two parts, Part 1 was the bioequivalence of daprodustat Tablets and part 2 was food effect on the pharmacokinetics (PK) of daprodustat.

Arm/Group Title	Part 1: Daprodustat 2mg*2+ Daprodustat 4mg*1	Part 1: Daprodustat 4mg*1 + Daprodustat 2mg*2	Part 2: Daprodustat 4mg*1 (Fed) + Daprodustat 4mg*1 (Fast)	Part 2: Daprodustat 4mg*1 (Fast) + Daprodustat 4mg*1 (Fed)
Arm/Group Description	Participants received a single dose Daprodustat 2 milligram (mg) two tablets followed by Daprodustat 4 mg single tablet, administered orally on Day 1.There was a washout period of at least 5 days between the 2 intervention periods.	Participants received a single dose Daprodustat 4 mg one tablet followed by Daprodustat 2 mg two tablets, administered orally on Day 1. There was a washout period of at least 5 days between the 2 intervention periods.	Participants received a single dose Daprodustat 4 mg one tablet in fed state followed by Daprodustat 4 mg one tablet as single dose in fasted state, administered orally on Day 1.There was a washout period of at least 5 days between the 2 treatment periods.	Participants received a single dose Daprodustat 4 mg one tablet in fasted state followed by Daprodustat 4 mg one tablet as single dose in fed state, administered orally on Day 1.There was a washout period of at least 5 days between the 2 treatment periods.
Period Title: Part 1, Intervention Period 1 (2 Days)
STARTED	26	26	0	0
COMPLETED	26	26	0	0
NOT COMPLETED	0	0	0	0
Period Title: Part 1, Intervention Period 1 (2 Days)
STARTED	26	26	0	0
COMPLETED	26	25	0	0
NOT COMPLETED	0	1	0	0
Period Title: Part 1, Intervention Period 1 (2 Days)
STARTED	26	25	0	0
COMPLETED	26	25	0	0
NOT COMPLETED	0	0	0	0
Period Title: Part 1, Intervention Period 1 (2 Days)
STARTED	0	0	6	6
COMPLETED	0	0	6	6
NOT COMPLETED	0	0	0	0
Period Title: Part 1, Intervention Period 1 (2 Days)
STARTED	0	0	6	6
COMPLETED	0	0	6	6
NOT COMPLETED	0	0	0	0
Period Title: Part 1, Intervention Period 1 (2 Days)
STARTED	0	0	6	6
COMPLETED	0	0	6	6
NOT COMPLETED	0	0	0	0

Baseline Characteristics

Arm/Group Title	Total Participants Part 1	Total Participants Part 2	Total
Arm/Group Description	Participants received daprodustat 2mg*2 tablets and daprodustat 4mg*1 tablets (fasted state) in either of the two treatment periods separated by a washout of at least 5 days between the two treatment periods.	Participants received daprodustat 4mg*1 tablet (fed state) and daprodustat 4mg*1 tablet (fasted state) in either of the two treatment periods separated by a washout of at least 5 days between the two treatment periods.	Total of all reporting groups
Overall Participants	52	12	64
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	27.9 (6.91)	30.0 (7.51)	28.3 (7.01)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	52 100%	12 100%	64 100%
Race/Ethnicity, Customized (Number) [Number]
Asian -Japanese Heritage	52 100%	12 100%	64 100%

Outcome Measures

1. Primary Outcome

Title	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
Description	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.
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

Outcome Measure Data

Analysis Population Description

PK Population

Arm/Group Title	Part 1: Daprodustat 2mg*2	Part 1: Daprodustat 4mg*1
Arm/Group Description	Participants received a single dose of daprodustat 2mg*2 tablets, administered orally in fasted state on Day 1 in either of period 1 and Period 2 as per the randomization schedule	Participants received single dose of Daprodustat 4mg one tablet, administered orally in fasted state on Day 1 in either of Period 1 and Period 2 as per randomization schedule
Measure Participants	51	52
AUC (0-t)	182.8420 (30.7)	179.6940 (30.4)
AUC (0-inf)	183.0240 (30.7)	179.8710 (30.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 1: Daprodustat 2mg*2, Part 1: Daprodustat 4mg*1
	Comments
	Type of Statistical Test	Equivalence
	Comments	If the 90% CI of the ratio of geometric mean doesn't fall within a range of 0.80 to 1.25 i.e., null hypothesis is not rejected the bioequivalence is established if the point estimate falls within a range of 0.90 to 1.11
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio of geometric mean
	Estimated Value	1.02
	Confidence Interval	(2-Sided) 90%; 0.97 to 1.07
	Parameter Dispersion	Type: Value:
	Estimation Comments	AUC (0-t)

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Part 1: Daprodustat 2mg*2, Part 1: Daprodustat 4mg*1
	Comments
	Type of Statistical Test	Equivalence
	Comments	If the 90% CI of the ratio of geometric mean doesn't fall within a range of 0.80 to 1.25 i.e., null hypothesis is not rejected the bioequivalence is established if the point estimate falls within a range of 0.90 to 1.11
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio of geometric mean
	Estimated Value	1.02
	Confidence Interval	(2-Sided) 90%; 0.97 to 1.07
	Parameter Dispersion	Type: Value:
	Estimation Comments	AUC(0-inf)

2. Primary Outcome

Title	Part 1:Maximum Observed Drug Concentration (Cmax) of Daprodustat
Description	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.
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

Outcome Measure Data

Analysis Population Description

PK Population

Arm/Group Title	Part 1: Daprodustat 2mg*2	Part 1: Daprodustat 4mg*1
Arm/Group Description	Participants received a single dose of daprodustat 2mg*2 tablets, administered orally in fasted state on Day 1 in either of period 1 and Period 2 as per the randomization schedule	Participants received single dose of Daprodustat 4mg one tablet, administered orally in fasted state on Day 1 in either of Period 1 and Period 2 as per randomization schedule
Measure Participants	51	52
Geometric Mean (Geometric Coefficient of Variation) [Nanogram/milliliter]	88.8811 (37.0)	85.1365 (37.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 1: Daprodustat 2mg*2, Part 1: Daprodustat 4mg*1
	Comments
	Type of Statistical Test	Equivalence
	Comments	If the 90% CI of the ratio of geometric mean doesn't fall within a range of 0.80 to 1.25 i.e., null hypothesis is not rejected the bioequivalence is established if the point estimate falls within a range of 0.90 to 1.11
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio of geometric mean
	Estimated Value	1.04
	Confidence Interval	(2-Sided) 90%; 0.97 to 1.12
	Parameter Dispersion	Type: Value:
	Estimation Comments	Cmax

3. Primary Outcome

Title	Part 1:Terminal Phase Half-life (T1/2) of Daprodustat and Mean Residence Time (MRT)
Description	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.
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

Outcome Measure Data

Analysis Population Description

PK Population

Arm/Group Title	Part 1: Daprodustat 2mg*2	Part 1: Daprodustat 4mg*1
Arm/Group Description	Participants received a single dose of daprodustat 2mg*2 tablets, administered orally in fasted state on Day 1 in either of period 1 and Period 2 as per the randomization schedule	Participants received single dose of Daprodustat 4mg one tablet, administered orally in fasted state on Day 1 in either of Period 1 and Period 2 as per randomization schedule
Measure Participants	51	52
t1/2	3.2427 (14.9)	3.2579 (11.8)
MRT	2.8142 (25.9)	2.9637 (23.2)

4. Primary Outcome

Title	Part 1: Time of Occurrence of Cmax (Tmax) of Daprodustat
Description	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.
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

Outcome Measure Data

Analysis Population Description

PK Population

Arm/Group Title	Part 1: Daprodustat 2mg*2	Part 1: Daprodustat 4mg*1
Arm/Group Description	Participants received a single dose of daprodustat 2mg*2 tablets, administered orally in fasted state on Day 1 in either of period 1 and Period 2 as per the randomization schedule	Participants received single dose of Daprodustat 4mg one tablet, administered orally in fasted state on Day 1 in either of Period 1 and Period 2 as per randomization schedule
Measure Participants	51	52
Median (Full Range) [hour]	2.000	2.000

5. Primary Outcome

Title	Part 1: Percentage of AUC (0-inf) Obtained by Extrapolation (Percentage AUCex)
Description	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.
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

Outcome Measure Data

Analysis Population Description

PK Population

Arm/Group Title	Part 1: Daprodustat 2mg*2	Part 1: Daprodustat 4mg*1
Arm/Group Description	Participants received a single dose of daprodustat 2mg*2 tablets, administered orally in fasted state on Day 1 in either of period 1 and Period 2 as per the randomization schedule	Participants received single dose of Daprodustat 4mg one tablet, administered orally in fasted state on Day 1 in either of Period 1 and Period 2 as per randomization schedule
Measure Participants	51	52
Geometric Mean (Geometric Coefficient of Variation) [Percentage of AUCex]	0.0862 (53.5)	0.0836 (55.3)

6. Primary Outcome

Title	Part 1:Apparent Clearance (CL/F) of Daprodustat
Description	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.
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

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Part 1: Daprodustat 2mg*2	Part 1: Daprodustat 4mg*1
Arm/Group Description	Participants received a single dose of daprodustat 2mg*2 tablets, administered orally in fasted state on Day 1 in either of period 1 and Period 2 as per the randomization schedule	Participants received single dose of Daprodustat 4mg one tablet, administered orally in fasted state on Day 1 in either of Period 1 and Period 2 as per randomization schedule
Measure Participants	51	52
Geometric Mean (Geometric Coefficient of Variation) [Liters per hour]	21.8551 (30.7)	22.2382 (30.4)

7. Primary Outcome

Title	Part 1:Apparent Oral Volume of Distribution (Vz/F) of Daprodustat
Description	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.
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

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Part 1: Daprodustat 2mg*2	Part 1: Daprodustat 4mg*1
Arm/Group Description	Participants received a single dose of daprodustat 2mg*2 tablets, administered orally in fasted state on Day 1 in either of period 1 and Period 2 as per the randomization schedule	Participants received single dose of Daprodustat 4mg one tablet, administered orally in fasted state on Day 1 in either of Period 1 and Period 2 as per randomization schedule
Measure Participants	51	52
Geometric Mean (Geometric Coefficient of Variation) [Milliliters (mL)]	102244.3 (33.2)	104522.8 (30.8)

8. Primary Outcome

Title	Part 1: Elimination Rate Constant (Kel) of Daprodustat
Description	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.
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

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Part 1: Daprodustat 2mg*2	Part 1: Daprodustat 4mg*1
Arm/Group Description	Participants received a single dose of daprodustat 2mg*2 tablets, administered orally in fasted state on Day 1 in either of period 1 and Period 2 as per the randomization schedule	Participants received single dose of Daprodustat 4mg one tablet, administered orally in fasted state on Day 1 in either of Period 1 and Period 2 as per randomization schedule
Measure Participants	51	52
Geometric Mean (Geometric Coefficient of Variation) [Per hour]	0.2138 (14.9)	0.2128 (11.8)

9. Primary Outcome

Title	Part 2:AUC[0-t] andAUC [0-inf] of Daprodustat
Description	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.
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

Outcome Measure Data

Analysis Population Description

PK Population

Arm/Group Title	Daprodustat 4mg (Fed)	Daprodustat 4mg(Fasted)
Arm/Group Description	Participants received a single dose of daprodustat 4mg one tablet, administered orally in fed state on Day 1 in intervention period 1	Participants received single dose of daprodustat 4mg one tablet, administered orally in fasted state on Day 1 in intervention Period 2
Measure Participants	12	12
AUC (0-t)	142.9556 (18.0)	156.4222 (19.3)
AUC (0-inf)	143.1156 (18.0)	156.5481 (19.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 1: Daprodustat 2mg*2, Part 1: Daprodustat 4mg*1
	Comments
	Type of Statistical Test	Equivalence
	Comments	If the 90% CI of the ratio of geometric mean doesn't fall within a range of 0.80 to 1.25 i.e., null hypothesis is not rejected the bioequivalence is established if the point estimate falls within a range of 0.90 to 1.11
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio of geometric mean
	Estimated Value	0.91
	Confidence Interval	(2-Sided) 90%; 0.82 to 1.01
	Parameter Dispersion	Type: Value:
	Estimation Comments	AUC (0-t)

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Part 1: Daprodustat 2mg*2, Part 1: Daprodustat 4mg*1
	Comments
	Type of Statistical Test	Equivalence
	Comments	If the 90% CI of the ratio of geometric mean doesn't fall within a range of 0.80 to 1.25 i.e., null hypothesis is not rejected the bioequivalence is established if the point estimate falls within a range of 0.90 to 1.11
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio of geometric mean
	Estimated Value	0.91
	Confidence Interval	(2-Sided) 90%; 0.82 to 1.01
	Parameter Dispersion	Type: Value:
	Estimation Comments	AUC (0-inf)

10. Primary Outcome

Title	Part 2: Cmax of Daprodustat
Description	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.
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

Outcome Measure Data

Analysis Population Description

PK Population

Arm/Group Title	Daprodustat 4mg Fed	Daprodustat 4mg Fasted
Arm/Group Description	Participants received a single dose of daprodustat 4mg one tablet, administered orally in fed state on Day 1 in intervention period 1	Participants received single dose of daprodustat 4mg one tablet, administered orally in fasted state on Day 1 in intervention Period 2
Measure Participants	12	12
Geometric Mean (Geometric Coefficient of Variation) [Nanogram/milliliter (ng/L)]	67.8240 (26.7)	76.1944 (29.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 1: Daprodustat 2mg*2, Part 1: Daprodustat 4mg*1
	Comments
	Type of Statistical Test	Equivalence
	Comments	If the 90% CI of the ratio of geometric mean doesn't fall within a range of 0.80 to 1.25 i.e., null hypothesis is not rejected the bioequivalence is established if the point estimate falls within a range of 0.90 to 1.11
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio of geomtric mean
	Estimated Value	0.89
	Confidence Interval	() 90%; 0.73 to 1.08
	Parameter Dispersion	Type: Value:
	Estimation Comments

11. Primary Outcome

Title	Part 2: T1/2 and MRT of Daprodustat
Description	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.
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

Outcome Measure Data

Analysis Population Description

PK Population

Arm/Group Title	Daprodustat 4mg Fed	Part 2: Daprodustat 4mg Fasted
Arm/Group Description	Participants received a single dose of daprodustat 4mg one tablet, administered orally in fed state on Day 1 in intervention period 1	Participants received single dose of daprodustat 4mg one tablet, administered orally in fasted state on Day 1 in intervention Period 2
Measure Participants	12	12
t1/2	3.2160 (9.7)	3.2389 (8.0)
MRT	3.2420 (25.2)	2.6695 (26.8)

12. Primary Outcome

Title	Part 2: Tmax of Daprodustat
Description	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.
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

Outcome Measure Data

Analysis Population Description

PK Population.

Arm/Group Title	Part 2: Daprodustat 4mg Fed	Part 2: Daprodustat 4mg Fasted
Arm/Group Description	Participants received a single dose of daprodustat 4mg one tablet, administered orally in fed state on Day 1 in intervention period 1	Participants received single dose of daprodustat 4mg one tablet, administered orally in fasted state on Day 1 in intervention Period 2
Measure Participants	12	12
Median (Full Range) [hour]	2.750	1.750

13. Primary Outcome

Title	Part 2: Percentage AUCex of Dapordustat
Description	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.
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

Outcome Measure Data

Analysis Population Description

PK Population.

Arm/Group Title	Part 2: Daprodustat 4mg Fed	Part 2: Daprodustat 4mg Fasted
Arm/Group Description	Participants received a single dose of daprodustat 2mg*2 tablets, administered orally in fasted state on Day 1 in either of period 1 and Period 2 as per the randomization schedule	Participants received single dose of daprodustat 4mg one tablet, administered orally in fasted state on Day 1 in intervention Period 2
Measure Participants	12	12
Geometric Mean (Geometric Coefficient of Variation) [Percentage of AUCex]	0.1071 (30.9)	0.0723 (47.9)

14. Primary Outcome

Title	Part 2: CL/F of Daprodustat
Description	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.
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

Outcome Measure Data

Analysis Population Description

PK Population.

Arm/Group Title	Part 2: Daprodustat 4mg Fed	Part 2: Daprodustat 4mg Fasted
Arm/Group Description	Participants received a single dose of daprodustat 2mg*2 tablets, administered orally in fasted state on Day 1 in either of period 1 and Period 2 as per the randomization schedule	Participants received single dose of daprodustat 4mg one tablet, administered orally in fasted state on Day 1 in intervention Period 2
Measure Participants	12	12
Geometric Mean (Geometric Coefficient of Variation) [Liters per hour]	27.9494 (18.0)	25.5512 (19.2)

15. Primary Outcome

Title	Part 2: Vz/F of Daprodustat
Description	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.
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

Outcome Measure Data

Analysis Population Description

PK Population.

Arm/Group Title	Part 2: Daprodustat 4mg Fed	Part 2: Daprodustat 4mg Fasted
Arm/Group Description	Participants received a single dose of daprodustat 2mg*2 tablets, administered orally in fasted state on Day 1 in either of period 1 and Period 2 as per the randomization schedule	Participants received single dose of daprodustat 4mg one tablet, administered orally in fasted state on Day 1 in intervention Period 2
Measure Participants	12	12
Geometric Mean (Geometric Coefficient of Variation) [Milliliters (mL)]	129676.9 (18.7)	119394.6 (19.7)

16. Primary Outcome

Title	Part 2: Kel of Daprodustat
Description	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.
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

Outcome Measure Data

Analysis Population Description

PK Population.

Arm/Group Title	Part 2: Daprodustat 4mg Fed	Part 2: Daprodustat 4mg Fasted
Arm/Group Description	Participants received a single dose of daprodustat 2mg*2 tablets, administered orally in fasted state on Day 1 in either of period 1 and Period 2 as per the randomization schedule	Participants received single dose of daprodustat 4mg one tablet, administered orally in fasted state on Day 1 in intervention Period 2
Measure Participants	12	12
Geometric Mean (Geometric Coefficient of Variation) [Per hour]	0.2155 (9.7)	0.2140 (8.0)

17. Secondary Outcome

Title	Part 1: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description	AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect or is medically significant. Safety population comprised of all randomized participants who took at least one dose of study treatment.
Time Frame	Up to Day 16

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Part 1: Daprodustat 2mg*2	Part 1: Daprodustat 4mg*1
Arm/Group Description	Participants received a single dose of daprodustat 2mg*2 tablets, administered orally in fasted state on Day 1 in either of period 1 and Period 2 as per the randomization schedule	Participants received single dose of Daprodustat 4mg one tablet, administered orally in fasted state on Day 1 in either of Period 1 and Period 2 as per randomization schedule
Measure Participants	51	52
Any AE	3 5.8%	1 8.3%
Any SAE	0 0%	0 0%

18. Secondary Outcome

Title	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.
Description	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.
Time Frame	Baseline (Day -1), 24hours post-dose

Outcome Measure Data

Analysis Population Description

Safety Population.

Arm/Group Title	Part 1: Daprodustat 2mg*2	Part 1: Daprodustat 4mg*1
Arm/Group Description	Participants received a single dose of daprodustat 2mg*2 tablets, administered orally in fasted state on Day 1 in either of period 1 and Period 2 as per the randomization schedule	Participants received single dose of Daprodustat 4mg one tablet, administered orally in fasted state on Day 1 in either of Period 1 and Period 2 as per randomization schedule
Measure Participants	51	52
Glucose 24hours	-0.007619 (0.3094690)	-0.004270 (0.3243933)
Calcium 24hours	-0.016144 (0.0694710)	-0.015834 (0.0623072)
Cholesterol 24hours	-0.043607 (0.3197656)	0.046747 (0.2952955)
Chloride 24hours	0.9 (1.74)	0.5 (1.63)
HDL cholesterol 24hours	-0.128793 (0.1230991)	-0.111397 (0.1067511)
LDL cholesterol 24hours	0.022818 (0.2151606)	0.099462 (0.2265669)
Potassium 24hours	0.04 (0.295)	0.03 (0.272)
Phosphate 24hours	-0.102568 (0.1114273)	-0.091281 (0.1110710)
Sodium 24hours	0.2 (1.37)	0.0 (1.50)
Triglycerides 24hours	0.21802 (0.273901)	0.16385 (0.274955)
Urea 24hours	-0.14000 (0.767902)	-0.29178 (0.840240)

19. Secondary Outcome

Title	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).
Description	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.
Time Frame	Baseline (Day -1), 24hours post-dose

Outcome Measure Data

Analysis Population Description

Safety Population.

Arm/Group Title	Part 1: Daprodustat 2mg*2	Part 1: Daprodustat 4mg*1
Arm/Group Description	Participants received a single dose of daprodustat 2mg*2 tablets, administered orally in fasted state on Day 1 in either of period 1 and Period 2 as per the randomization schedule	Participants received single dose of Daprodustat 4mg one tablet, administered orally in fasted state on Day 1 in either of Period 1 and Period 2 as per randomization schedule
Measure Participants	51	52
ALP 24hours	-9.5 (17.24)	-10.8 (12.83)
ALT 24hours	-2.0 (3.65)	-1.0 (3.19)
AST 24hours	-2.1 (3.19)	-1.8 (3.22)
Creatine kinase 24hours	-33.9 (28.73)	-32.3 (30.24)
GGT 24hours	-1.6 (2.34)	-1.1 (1.34)
Lactate dehydrogenase 24hours	-20.5 (12.30)	-19.2 (9.15)

20. Secondary Outcome

Title	Part 1: Change From Baseline in Chemistry Parameters; Albumin, Protein.
Description	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.
Time Frame	Baseline (Day -1), 24hours post-dose

Outcome Measure Data

Analysis Population Description

Safety Population.

Arm/Group Title	Part 1: Daprodustat 2mg*2	Part 1: Daprodustat 4mg*1
Arm/Group Description	Participants received a single dose of daprodustat 2mg*2 tablets, administered orally in fasted state on Day 1 in either of period 1 and Period 2 as per the randomization schedule	Participants received single dose of Daprodustat 4mg one tablet, administered orally in fasted state on Day 1 in either of Period 1 and Period 2 as per randomization schedule
Measure Participants	51	52
Albumin 24hours	-2.0 (1.74)	-2.0 (1.69)
Protein 24hours	-2.3 (2.90)	-2.1 (2.35)

21. Secondary Outcome

Title	Part 1: Change From Baseline in Chemistry Parameters; Direct Bilirubin, Bilirubin, Creatinine, Urate
Description	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.
Time Frame	Baseline (Day -1), 24hours post-dose

Outcome Measure Data

Analysis Population Description

Safety Population.

Arm/Group Title	Part 1: Daprodustat 2mg*2	Part 1: Daprodustat 4mg*1
Arm/Group Description	Participants received a single dose of daprodustat 2mg*2 tablets, administered orally in fasted state on Day 1 in either of period 1 and Period 2 as per the randomization schedule	Participants received single dose of Daprodustat 4mg one tablet, administered orally in fasted state on Day 1 in either of Period 1 and Period 2 as per randomization schedule
Measure Participants	51	52
Direct bilirubin 24hours	0.268 (0.7151)	0.164 (0.6989)
Bilirubin 24hours	2.615 (5.0537)	2.960 (4.7784)
Creatinine 24hours	1.7160 (4.18539)	1.4110 (4.84901)
Urate 24hours	26.1245 (28.30344)	25.6222 (28.35581)

22. Secondary Outcome

Title	Part 1:Change From Baseline in Hematology Parameter; Hematocrit
Description	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.
Time Frame	Baseline (Day -1), 24hours post-dose

Outcome Measure Data

Analysis Population Description

Safety Population.

Arm/Group Title	Part 1: Daprodustat 2mg*2	Part 1: Daprodustat 4mg*1
Arm/Group Description	Participants received a single dose of daprodustat 2mg*2 tablets, administered orally in fasted state on Day 1 in either of period 1 and Period 2 as per the randomization schedule	Participants received single dose of Daprodustat 4mg one tablet, administered orally in fasted state on Day 1 in either of Period 1 and Period 2 as per randomization schedule
Measure Participants	51	52
Mean (Standard Deviation) [Proportion of red blood cells in blood]	0.0005 (0.01593)	0.0014 (0.01464)

23. Secondary Outcome

Title	Part 1:Change From Baseline in Hematology Parameter; Reticulocytes
Description	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.
Time Frame	Baseline (Day -1), 24hours post-dose

Outcome Measure Data

Analysis Population Description

Safety Population.

Arm/Group Title	Part 1: Daprodustat 2mg*2	Part 1: Daprodustat 4mg*1
Arm/Group Description	Participants received a single dose of daprodustat 2mg*2 tablets, administered orally in fasted state on Day 1 in either of period 1 and Period 2 as per the randomization schedule	Participants received single dose of Daprodustat 4mg one tablet, administered orally in fasted state on Day 1 in either of Period 1 and Period 2 as per randomization schedule
Measure Participants	51	52
Mean (Standard Deviation) [Praportion of reticulocytes in blood]	-0.0005 (0.00179)	-0.0001 (0.00189)

24. Secondary Outcome

Title	Part 1: Change From Baseline in Hematology Parameters; Hemoglobin (Hb), Erythrocyte Mean Corpuscular Hb Concentration (MCHC)
Description	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.
Time Frame	Baseline (Day -1), 24hours post-dose

Outcome Measure Data

Analysis Population Description

Safety Population.

Arm/Group Title	Part 1: Daprodustat 2mg*2	Part 1: Daprodustat 4mg*1
Arm/Group Description	Participants received a single dose of daprodustat 2mg*2 tablets, administered orally in fasted state on Day 1 in either of period 1 and Period 2 as per the randomization schedule	Participants received single dose of Daprodustat 4mg one tablet, administered orally in fasted state on Day 1 in either of Period 1 and Period 2 as per randomization schedule
Measure Participants	51	52
Hb 24hours	1.1 (5.81)	0.8 (4.99)
MCHC 24hours	2.1 (4.23)	0.8 (4.99)

25. Secondary Outcome

Title	Part 1: Change From Baseline in Hematology Parameters; Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils
Description	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.
Time Frame	Baseline (Day -1), 24hours post-dose

Outcome Measure Data

Analysis Population Description

Safety Population.

Arm/Group Title	Part 1: Daprodustat 2mg*2	Part 1: Daprodustat 4mg*1
Arm/Group Description	Participants received a single dose of daprodustat 2mg*2 tablets, administered orally in fasted state on Day 1 in either of period 1 and Period 2 as per the randomization schedule	Participants received single dose of Daprodustat 4mg one tablet, administered orally in fasted state on Day 1 in either of Period 1 and Period 2 as per randomization schedule
Measure Participants	51	52
Basophils 24hours	-0.01 (0.173)	0.00 (0.197)
Eosinophils 24hours	0.27 (0.871)	0.25 (0.874)
Lymphocytes 24hours	-1.47 (6.070)	-0.86 (7.049)
Monocytes 24hours	-0.43 (1.293)	-0.33 (1.108)
Neutrophils 24hours	1.64 (6.407)	0.94 (7.480)

26. Secondary Outcome

Title	Part 1: Change From Baseline in Hematology Parameter Erythrocyte MCHC
Description	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.
Time Frame	Baseline (Day -1), 24hours post-dose

Outcome Measure Data

Analysis Population Description

Safety Population.

Arm/Group Title	Part 1: Daprodustat 2mg*2	Part 1: Daprodustat 4mg*1
Arm/Group Description	Participants received a single dose of daprodustat 2mg*2 tablets, administered orally in fasted state on Day 1 in either of period 1 and Period 2 as per the randomization schedule	Participants received single dose of Daprodustat 4mg one tablet, administered orally in fasted state on Day 1 in either of Period 1 and Period 2 as per randomization schedule
Measure Participants	51	52
Mean (Standard Deviation) [Picograms (pg)]	0.11 (0.331)	0.01 (0.319)

27. Secondary Outcome

Title	Part 1: Change From Baseline in Hematology Parameter Erythrocyte Mean Corpuscular Volume (EMCV)
Description	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.
Time Frame	Baseline (Day -1), 24hours post-dose

Outcome Measure Data

Analysis Population Description

Safety Population.

Arm/Group Title	Part 1: Daprodustat 2mg*2	Part 1: Daprodustat 4mg*1
Arm/Group Description	Participants received a single dose of daprodustat 2mg*2 tablets, administered orally in fasted state on Day 1 in either of period 1 and Period 2 as per the randomization schedule	Participants received single dose of Daprodustat 4mg one tablet, administered orally in fasted state on Day 1 in either of Period 1 and Period 2 as per randomization schedule
Measure Participants	51	52
Mean (Standard Deviation) [Femtoliters]	-0.2 (0.75)	-0.2 (0.83)

28. Secondary Outcome

Title	Part 1: Change From Baseline in Hematology Parameters Platelets, Leukocytes
Description	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.
Time Frame	Baseline (Day -1), 24hours post-dose

Outcome Measure Data

Analysis Population Description

Safety Population.

Arm/Group Title	Part 1: Daprodustat 2mg*2	Part 1: Daprodustat 4mg*1
Arm/Group Description	Participants received a single dose of daprodustat 2mg*2 tablets, administered orally in fasted state on Day 1 in either of period 1 and Period 2 as per the randomization schedule	Participants received single dose of Daprodustat 4mg one tablet, administered orally in fasted state on Day 1 in either of Period 1 and Period 2 as per randomization schedule
Measure Participants	51	52
Platelets 24hours	0.7 (13.21)	2.0 (14.97)
Leukocytes 24hours	-0.55 (0.883)	-0.53 (0.928)

29. Secondary Outcome

Title	Part 1: Change From Baseline in Hematology Parameter: Erythrocytes
Description	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.
Time Frame	Baseline (Day -1), 24hours post-dose

Outcome Measure Data

Analysis Population Description

Safety Population.

Arm/Group Title	Part 1: Daprodustat 2mg*2	Part 1: Daprodustat 4mg*1
Arm/Group Description	Participants received a single dose of daprodustat 2mg*2 tablets, administered orally in fasted state on Day 1 in either of period 1 and Period 2 as per the randomization schedule	Participants received single dose of Daprodustat 4mg one tablet, administered orally in fasted state on Day 1 in either of Period 1 and Period 2 as per randomization schedule
Measure Participants	51	52
Mean (Standard Deviation) [Trillion cells/liter (10^12 cell/L)]	0.018 (0.1941)	0.023 (0.1771)

30. Secondary Outcome

Title	Part 1: Change From Baseline in Urinalysis Parameter; Potential of Hydrogen (pH)
Description	Urinary pH measurement is a routine part of urinalysis. Urine pH is an acid-base measurement. pH is measured on a numeric scale ranging from 0 to 14; values on the scale refer to the degree of alkalinity or acidity. A pH of 7 is neutral. A pH less than 7 is acidic, and a pH greater than 7 is basic. Normal urine has a slightly acid pH (5.0 - 6.0). Urine samples were collected for the measurement of urine pH by method up to 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.
Time Frame	Baseline (Day -1), 24hours post-dose

Outcome Measure Data

Analysis Population Description

Safety Population.

Arm/Group Title	Part 1: Daprodustat 2mg*2	Part 1: Daprodustat 4mg*1
Arm/Group Description	Participants received a single dose of daprodustat 2mg*2 tablets, administered orally in fasted state on Day 1 in either of period 1 and Period 2 as per the randomization schedule	Participants received single dose of Daprodustat 4mg one tablet, administered orally in fasted state on Day 1 in either of Period 1 and Period 2 as per randomization schedule
Measure Participants	51	52
Mean (Standard Deviation) [pH]	-0.04 (0.573)	-0.07 (0.714)

31. Secondary Outcome

Title	Part 1: Change From Baseline in Urinalysis Parameter; Specific Gravity
Description	Urinary specific gravity measurement is a routine part of urinalysis. Urine specific gravity is a measure of the concentration of solutes in the urine and provides information on the kidney's ability to concentrate urine. The concentration of the excreted molecules determines the urine's specific gravity. Urine samples were collected for the measurement of urine specific gravity by dipstick method up to 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.
Time Frame	Baseline (Day -1), 24hours post-dose

Outcome Measure Data

Analysis Population Description

Safety Population.

Arm/Group Title	Part 1: Daprodustat 2mg*2	Part 1: Daprodustat 4mg*1
Arm/Group Description	Participants received a single dose of daprodustat 2mg*2 tablets, administered orally in fasted state on Day 1 in either of period 1 and Period 2 as per the randomization schedule	Participants received single dose of Daprodustat 4mg one tablet, administered orally in fasted state on Day 1 in either of Period 1 and Period 2 as per randomization schedule
Measure Participants	51	52
Mean (Standard Deviation) [Kilogram per cubic meter]	0.0092 (0.00744)	0.0088 (0.00767)

32. Secondary Outcome

Title	Part 1: Change From Baseline in Vital Signs; Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)
Description	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.
Time Frame	Baseline (Day -1), 3 and 24 hours (post-dose)

Outcome Measure Data

Analysis Population Description

Safety Population.

Arm/Group Title	Part 1: Daprodustat 2mg*2	Part 1: Daprodustat 4mg*1
Arm/Group Description	Participants received a single dose of daprodustat 2mg*2 tablets, administered orally in fasted state on Day 1 in either of period 1 and Period 2 as per the randomization schedule	Participants received single dose of Daprodustat 4mg one tablet, administered orally in fasted state on Day 1 in either of Period 1 and Period 2 as per randomization schedule
Measure Participants	51	52
DBP 3hours	-2.9 (5.84)	-1.5 (7.00)
DBP 24hours	-1.8 (6.38)	0.1 (7.67)
SBP 3hours	-0.6 (7.48)	-0.4 (7.92)
SBP 24hours	-0.9 (8.07)	0.2 (8.93)

33. Secondary Outcome

Title	Part 1: Change From Baseline in Pulse Rate
Description	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.
Time Frame	Baseline (Day -1), 3 and 24 hours (post-dose)

Outcome Measure Data

Analysis Population Description

Safety Population.

Arm/Group Title	Part 1: Daprodustat 2mg*2	Part 1: Daprodustat 4mg*1
Arm/Group Description	Participants received a single dose of daprodustat 2mg*2 tablets, administered orally in fasted state on Day 1 in either of period 1 and Period 2 as per the randomization schedule	Participants received single dose of Daprodustat 4mg one tablet, administered orally in fasted state on Day 1 in either of Period 1 and Period 2 as per randomization schedule
Measure Participants	51	52
Pulse rate 3hours	0.0 (6.91)	0.7 (4.78)
Pulse rate 24hours	0.1 (6.04)	1.0 (5.12)

34. Secondary Outcome

Title	Part 1: Change From Baseline in Temperature
Description	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.
Time Frame	Baseline (Day -1), 3 and 24 hours (post-dose)

Outcome Measure Data

Analysis Population Description

Safety Population.

Arm/Group Title	Part 1: Daprodustat 2mg*2	Part 1: Daprodustat 4mg*1
Arm/Group Description	Participants received a single dose of daprodustat 2mg*2 tablets, administered orally in fasted state on Day 1 in either of period 1 and Period 2 as per the randomization schedule	Participants received single dose of Daprodustat 4mg one tablet, administered orally in fasted state on Day 1 in either of Period 1 and Period 2 as per randomization schedule
Measure Participants	51	52
Temperature 3hours	0.23 (0.256)	0.22 (0.311)
Temperature 24hours	0.10 (0.212)	0.05 (0.330)

35. Secondary Outcome

Title	Part 1: Change From Baseline in Electrocardiogram (ECG) Parameter; Mean Heart Rate (HR)
Description	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.
Time Frame	Baseline (Day -1), 3 and 24 hours (post-dose)

Outcome Measure Data

Analysis Population Description

Safety Population.

Arm/Group Title	Part 1: Daprodustat 2mg*2	Part 1: Daprodustat 4mg*1
Arm/Group Description	Participants received a single dose of daprodustat 2mg*2 tablets, administered orally in fasted state on Day 1 in either of period 1 and Period 2 as per the randomization schedule	Participants received single dose of Daprodustat 4mg one tablet, administered orally in fasted state on Day 1 in either of Period 1 and Period 2 as per randomization schedule
Measure Participants	51	52
Mean HR 3hours	0.6 (5.01)	0.2 (4.21)
Mean HR 24hours	1.2 (4.28)	0.8 (5.18)

36. Secondary Outcome

Title	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
Description	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.
Time Frame	Baseline (Day -1), 3 and 24 hours (post-dose)

Outcome Measure Data

Analysis Population Description

Safety Population.

Arm/Group Title	Part 1: Daprodustat 2mg*2	Part 1: Daprodustat 4mg*1
Arm/Group Description	Participants received a single dose of daprodustat 2mg*2 tablets, administered orally in fasted state on Day 1 in either of period 1 and Period 2 as per the randomization schedule	Participants received single dose of Daprodustat 4mg one tablet, administered orally in fasted state on Day 1 in either of Period 1 and Period 2 as per randomization schedule
Measure Participants	51	52
PR Interval, Aggregate 3hours	-3.3 (10.87)	-3.8 (9.40)
PR Interval, Aggregate 24hours	1.4 (8.13)	0.0 (12.55)
QRS Duration, Aggregate 3hours	-2.8 (6.50)	-1.5 (6.42)
QRS Duration, Aggregate 24hours	-1.6 (6.62)	0.2 (6.50)
QT interval, Aggregate 3hours	0.0 (20.31)	0.8 (17.63)
QT interval, Aggregate 24hours	-5.2 (17.42)	-5.3 (18.33)
QTcF interval, Aggregate 3hours	1.2 (14.98)	1.6 (14.73)
QtcF Interval, Aggregate 24hours	-2.4 (13.65)	-3.1 (13.70)

37. Secondary Outcome

Title	Part 2: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description	AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect or is medically significant. Safety population comprised of all randomized participants who took at least one dose of study treatment.
Time Frame	Up to Day 16

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Part 2: Daprodustat 4mg (Fed)	Part 2: Daprodustat 4mg (Fasted)
Arm/Group Description	Participants received a single dose of daprodustat 4mg one tablet, administered orally in fed state on Day 1 in intervention period 1, the washout between the 2 intervention periods was set to be ≥ 5 days	Participants received single dose of Daprodustat 4mg one tablet, administered orally in fasted state on Day 1 in intervention Period 2
Measure Participants	12	12
Any AE	0 0%	0 0%
Any SAE	0 0%	0 0%

38. Secondary Outcome

Title	Part 2: Change From Baseline Chemistry Parameters; Glucose, Calcium, Cholesterol, Chloride, HDL Cholesterol, LDL Cholesterol, Potassium, Phosphate, Sodium, Triglycerides, and Urea
Description	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.
Time Frame	Baseline (Day -1), 24 hours (post-dose)

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Part 2: Daprodustat 4mg (Fed)	Part 2: Daprodustat 4mg (Fasted)
Arm/Group Description	Participants received a single dose of daprodustat 4mg one tablet, administered orally in fed state on Day 1 in intervention period 1, the washout between the 2 intervention periods was set to be ≥ 5 days	Participants received single dose of Daprodustat 4mg one tablet, administered orally in fasted state on Day 1 in intervention Period 2
Measure Participants	12	12
Glucose, 24hours	-0.425577 (0.2902134)	-0.018503 (0.2530908)
Calcium, 24hours	-0.076929 (0.0515273)	-0.058217 (0.0595515)
Cholesterol, 24hours	-0.172400 (0.2567913)	-0.094820 (0.2225472)
Chloride, 24hours	1.5 (1.45)	2.1 (2.27)
HDL cholesterol, 24hours	-0.165935 (0.0995210)	-0.148695 (0.0826086)
LDL cholesterol, 24hours	-0.170245 (0.1823445)	-0.066805 (0.1724049)
Potassium, 24hours	0.06 (0.294)	0.19 (0.231)
Phosphate, 24hours	-0.029599 (0.0928311)	-0.080725 (0.1324212)
Sodium, 24hours	0.3 (2.35)	0.9 (1.38)
Triglycerides, 24hours	0.25331 (0.219827)	0.08475 (0.197228)
Urea, 24hours	0.19040 (0.552713)	-0.14875 (0.588353)

39. Secondary Outcome

Title	Part 2: Change From Baseline in Chemistry Paremeters; ALP, ALT, AST, Creatine Kinase, Lactate Dehydrogenase, GGT
Description	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.
Time Frame	Baseline (Day -1), 24 hours (post-dose)

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Part 2: Daprodustat 4mg (Fed)	Part 2: Daprodustat 4mg (Fasted)
Arm/Group Description	Participants received a single dose of daprodustat 4mg one tablet, administered orally in fed state on Day 1 in intervention period 1, the washout between the 2 intervention periods was set to be ≥ 5 days	Participants received single dose of Daprodustat 4mg one tablet, administered orally in fasted state on Day 1 in intervention Period 2
Measure Participants	12	12
ALP, 24hours	-18.9 (15.48)	-13.3 (10.54)
ALT, 24hours	-3.1 (2.43)	-3.5 (2.02)
AST, 24hours	-2.8 (2.18)	-2.7 (2.46)
Creatine kinase, 24hours	-28.3 (13.70)	-15.3 (17.56)
Lactate dehydrogenase, 24hours	-21.0 (9.68)	-18.4 (9.05)
GGT, 24hours	-1.0 (1.41)	-1.6 (2.11)

40. Secondary Outcome

Title	Part 2: Change From Baseline in Chemistry Parameters; Albumin, Protein
Description	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.
Time Frame	Baseline (Day -1), 24 hours (post-dose)

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Part 2: Daprodustat 4mg (Fed)	Part 2: Daprodustat 4mg (Fasted)
Arm/Group Description	Participants received a single dose of daprodustat 4mg one tablet, administered orally in fed state on Day 1 in intervention period 1, the washout between the 2 intervention periods was set to be ≥ 5 days	Participants received single dose of Daprodustat 4mg one tablet, administered orally in fasted state on Day 1 in intervention Period 2
Measure Participants	12	12
Albumin 24hours	-3.2 (1.34)	-1.9 (1.16)
Protein 24hours	-3.4 (2.94)	-2.6 (2.02)

41. Secondary Outcome

Title	Part 2: Change From Baseline in Chemistry Parameters; Direct Bilirubin, Bilirubin, Creatinine, Urate
Description	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.
Time Frame	Baseline (Day -1), 24 hours (post-dose)

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Part 2: Daprodustat 4mg (Fed)	Part 2: Daprodustat 4mg (Fasted)
Arm/Group Description	Participants received a single dose of daprodustat 4mg one tablet, administered orally in fed state on Day 1 in intervention period 1, the washout between the 2 intervention periods was set to be ≥ 5 days	Participants received single dose of Daprodustat 4mg one tablet, administered orally in fasted state on Day 1 in intervention Period 2
Measure Participants	12	12
Direct bilirubin, 24hours	0.000 (0.000)	0.000 (1.0312)
Bilirubin, 24hours	2.280 (5.2748)	1.425 (3.1643)
Creatinine, 24hours	-1.6207 (5.16603)	-1.1050 (5.68072)
Urate, 24hours	23.2963 (20.98470)	21.8093 (19.53615)

42. Secondary Outcome

Title	Part 2: Change From Baseline in Hematology Parameters; Hematocrit
Description	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.
Time Frame	Baseline (Day -1), 24 hours (post-dose)

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Part 2: Daprodustat 4mg (Fed)	Part 2: Daprodustat 4mg (Fasted)
Arm/Group Description	Participants received a single dose of daprodustat 4mg one tablet, administered orally in fed state on Day 1 in intervention period 1, the washout between the 2 intervention periods was set to be ≥ 5 days	Participants received single dose of Daprodustat 4mg one tablet, administered orally in fasted state on Day 1 in intervention Period 2
Measure Participants	12	12
Mean (Standard Deviation) [Praportion of red blood cells in blood]	-0.0052 (0.01629)	-0.0025 (0.01519)

43. Secondary Outcome

Title	Part 2: Change From Baseline in Hematology Parameters; Reticulocytes
Description	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.
Time Frame	Baseline (Day -1), 24 hours (post-dose)

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Part 2: Daprodustat 4mg (Fed)	Part 2: Daprodustat 4mg (Fasted)
Arm/Group Description	Participants received a single dose of daprodustat 4mg one tablet, administered orally in fed state on Day 1 in intervention period 1, the washout between the 2 intervention periods was set to be ≥ 5 days	Participants received single dose of Daprodustat 4mg one tablet, administered orally in fasted state on Day 1 in intervention Period 2
Measure Participants	12	12
Mean (Standard Deviation) [Praportion of reticulocytes in blood]	-0.0002 (0.00164)	-0.0010 (0.00186)

44. Secondary Outcome

Title	Part 2: Change From Baseline in Hematology Parameters; Hb, Erythrocyte MCHC
Description	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.
Time Frame	Baseline (Day -1), 24 hours (post-dose)

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Part 2: Daprodustat 4mg (Fed)	Part 2: Daprodustat 4mg (Fasted)
Arm/Group Description	Participants received a single dose of daprodustat 4mg one tablet, administered orally in fed state on Day 1 in intervention period 1, the washout between the 2 intervention periods was set to be ≥ 5 days	Participants received single dose of Daprodustat 4mg one tablet, administered orally in fasted state on Day 1 in intervention Period 2
Measure Participants	12	12
Hb 24hours	-2.1 (5.28)	-1.2 (5.37)
EMCH concentration 24hours	0.4 (5.55)	-0.6 (4.66)

45. Secondary Outcome

Title	Part 2: Change From Baseline in Hematology Parameters; Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils
Description	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.
Time Frame	Baseline (Day -1), 24 hours (post-dose)

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Part 2: Daprodustat 4mg (Fed)	Part 2: Daprodustat 4mg (Fasted)
Arm/Group Description	Participants received a single dose of daprodustat 4mg one tablet, administered orally in fed state on Day 1 in intervention period 1, the washout between the 2 intervention periods was set to be ≥ 5 days	Participants received single dose of Daprodustat 4mg one tablet, administered orally in fasted state on Day 1 in intervention Period 2
Measure Participants	12	12
Basophils, 24hours	-0.04 (0.193)	-0.17 (0.239)
Eosinophils, 24hours	0.62 (1.620)	-0.49 (0.312)
Lymphocytes, 24hours	-2.31 (3.815)	-1.14 (6.015)
Monocytes, 24hours	-0.38 (0.732)	-0.03 (1.414)
Neutrophils, 24hours	2.12 (5.072)	1.83 (5.829)

46. Secondary Outcome

Title	Part 2: Change From Baseline in Hematology Parameter: EMCH
Description	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.
Time Frame	Baseline (Day -1), 24 hours (post-dose)

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Part 2: Daprodustat 4mg (Fed)	Part 2: Daprodustat 4mg (Fasted)
Arm/Group Description	Participants received a single dose of daprodustat 4mg one tablet, administered orally in fed state on Day 1 in intervention period 1, the washout between the 2 intervention periods was set to be ≥ 5 days	Participants received single dose of Daprodustat 4mg one tablet, administered orally in fasted state on Day 1 in intervention Period 2
Measure Participants	12	12
Mean (Standard Deviation) [picograms]	0.10 (0.413)	0.03 (0.311)

47. Secondary Outcome

Title	Part 2: Change From Baseline in Hematology Parameter EMCV
Description	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.
Time Frame	Baseline (Day -1), 24 hours (post-dose)

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Part 2: Daprodustat 4mg (Fed)	Part 2: Daprodustat 4mg (Fasted)
Arm/Group Description	Participants received a single dose of daprodustat 4mg one tablet, administered orally in fed state on Day 1 in intervention period 1, the washout between the 2 intervention periods was set to be ≥ 5 days	Participants received single dose of Daprodustat 4mg one tablet, administered orally in fasted state on Day 1 in intervention Period 2
Measure Participants	12	12
Mean (Standard Deviation) [Femtoliters]	0.5 (0.67)	0.3 (0.97)

48. Secondary Outcome

Title	Part 2: Change From Baseline in Hematology Parameters Platelets, Leukocytes
Description	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.
Time Frame	Baseline (Day -1), 24 hours (post-dose)

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Part 2: Daprodustat 4mg (Fed)	Part 2: Daprodustat 4mg (Fasted)
Arm/Group Description	Participants received a single dose of daprodustat 4mg one tablet, administered orally in fed state on Day 1 in intervention period 1, the washout between the 2 intervention periods was set to be ≥ 5 days	Participants received single dose of Daprodustat 4mg one tablet, administered orally in fasted state on Day 1 in intervention Period 2
Measure Participants	12	12
Platelets, 24hours	-10.9 (11.19)	-3.2 (12.04)
Leukocytes, 24hours	-0.27 (0.780)	-0.39 (0.579)

49. Secondary Outcome

Title	Part 2: Change From Baseline in Hematology Parameter Erythrocytes
Description	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.
Time Frame	Baseline (Day -1), 24 hours (post-dose)

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Part 2: Daprodustat 4mg (Fed)	Part 2: Daprodustat 4mg (Fasted)
Arm/Group Description	Participants received a single dose of daprodustat 4mg one tablet, administered orally in fed state on Day 1 in intervention period 1, the washout between the 2 intervention periods was set to be ≥ 5 days	Participants received single dose of Daprodustat 4mg one tablet, administered orally in fasted state on Day 1 in intervention Period 2
Measure Participants	12	12
Mean (Standard Deviation) [Trillion cells/liter (10^12 cell/L)]	-0.083 (0.1859)	-0.044 (0.1767)

50. Secondary Outcome

Title	Part 2: Change From Baseline in Urinalysis Parameter; Potential of Hydrogen (pH)
Description	Urinary pH measurement is a routine part of urinalysis. Urine pH is an acid-base measurement. pH is measured on a numeric scale ranging from 0 to 14; values on the scale refer to the degree of alkalinity or acidity. A pH of 7 is neutral. A pH less than 7 is acidic, and a pH greater than 7 is basic. Normal urine has a slightly acid pH (5.0 - 6.0). Urine samples were collected for the measurement of urine pH by method up to 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.
Time Frame	Baseline (Day -1), 24 hours (post-dose)

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Part 2: Daprodustat 4mg (Fed)	Part 2: Daprodustat 4mg (Fasted)
Arm/Group Description	Participants received a single dose of daprodustat 4mg one tablet, administered orally in fed state on Day 1 in intervention period 1, the washout between the 2 intervention periods was set to be ≥ 5 days	Participants received single dose of Daprodustat 4mg one tablet, administered orally in fasted state on Day 1 in intervention Period 2
Measure Participants	12	12
Mean (Standard Deviation) [pH]	0.13 (0.433)	0.13 (0.608)

51. Secondary Outcome

Title	Part 2: Change From Baseline in Urinalysis Parameter; Specific Gravity
Description	Urinary specific gravity measurement is a routine part of urinalysis. Urine specific gravity is a measure of the concentration of solutes in the urine and provides information on the kidney's ability to concentrate urine. The concentration of the excreted molecules determines the urine's specific gravity. Urine samples were collected for the measurement of urine specific gravity by dipstick method up to 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.
Time Frame	Baseline (Day -1), 24 hours (post-dose)

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Part 2: Daprodustat 4mg (Fed)	Part 2: Daprodustat 4mg (Fasted)
Arm/Group Description	Participants received a single dose of daprodustat 4mg one tablet, administered orally in fed state on Day 1 in intervention period 1, the washout between the 2 intervention periods was set to be ≥ 5 days	Participants received single dose of Daprodustat 4mg one tablet, administered orally in fasted state on Day 1 in intervention Period 2
Measure Participants	12	12
Mean (Standard Deviation) [Kilogram per cubic meter]	0.0054 (0.01215)	0.0013 (0.00900)

52. Secondary Outcome

Title	Part 2: Change From Baseline in Vital Signs; Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)
Description	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.
Time Frame	Baseline (Day -1),3 and 24hours (pre-dose)

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Part 2: Daprodustat 4mg (Fed)	Part 2: Daprodustat 4mg (Fasted)
Arm/Group Description	Participants received a single dose of daprodustat 4mg one tablet, administered orally in fed state on Day 1 in intervention period 1, the washout between the 2 intervention periods was set to be ≥ 5 days	Participants received single dose of Daprodustat 4mg one tablet, administered orally in fasted state on Day 1 in intervention Period 2
Measure Participants	12	12
DBP, 3hours	-4.8 (4.90)	0.2 (5.61)
DBP, 24hours	-0.6 (7.14)	2.8 (6.97)
SBP, 3hours	0.7 (6.10)	-1.3 (8.41)
SBP, 24hours	1.4 (6.93)	1.3 (5.18)

53. Secondary Outcome

Title	Part 2: Change From Baseline in Pulse Rate
Description	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.
Time Frame	Baseline (Day -1),3 and 24hours (pre-dose)

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Part 2: Daprodustat 4mg (Fed)	Part 2: Daprodustat 4mg (Fasted)
Arm/Group Description	Participants received a single dose of daprodustat 4mg one tablet, administered orally in fed state on Day 1 in intervention period 1, the washout between the 2 intervention periods was set to be ≥ 5 days	Participants received single dose of Daprodustat 4mg one tablet, administered orally in fasted state on Day 1 in intervention Period 2
Measure Participants	12	12
Pulse rate, 3hours	6.1 (5.37)	-1.5 (5.82)
Pulse rate, 24hours	4.0 (5.24)	2.9 (6.05)

54. Secondary Outcome

Title	Part 2: Change From Baseline in Temperature
Description	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.
Time Frame	Baseline (Day -1),3 and 24hours (pre-dose)

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Part 2: Daprodustat 4mg (Fed)	Part 2: Daprodustat 4mg (Fasted)
Arm/Group Description	Participants received a single dose of daprodustat 4mg one tablet, administered orally in fed state on Day 1 in intervention period 1, the washout between the 2 intervention periods was set to be ≥ 5 days	Participants received single dose of Daprodustat 4mg one tablet, administered orally in fasted state on Day 1 in intervention Period 2
Measure Participants	12	12
Temperature, 3hours	0.28 (0.302)	0.13 (0.293)
Temperature, 24hours	0.02 (0.424)	0.03 (0.245)

55. Secondary Outcome

Title	Part 2: Change From Baseline in ECG Parameter; Mean Heart Rate (HR)
Description	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.
Time Frame	Baseline (Day -1),3 and 24hours (pre-dose)

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Part 2: Daprodustat 4mg (Fed)	Part 2: Daprodustat 4mg (Fasted)
Arm/Group Description	Participants received a single dose of daprodustat 4mg one tablet, administered orally in fed state on Day 1 in intervention period 1, the washout between the 2 intervention periods was set to be ≥ 5 days	Participants received single dose of Daprodustat 4mg one tablet, administered orally in fasted state on Day 1 in intervention Period 2
Measure Participants	12	12
Mean HR, 3hours	3.7 (6.18)	0.0 (4.07)
Mean HR, 24hours	3.1 (6.60)	0.6 (4.72)

56. Secondary Outcome

Title	Part 2: Change From Baseline in ECG Parameter; PR Interval, QRS Interval, QT Interval, QTcF Interval
Description	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.
Time Frame	Baseline (Day -1),3 and 24hours (pre-dose)

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Part 2: Daprodustat 4mg (Fed)	Part 2: Daprodustat 4mg (Fasted)
Arm/Group Description	Participants received a single dose of daprodustat 4mg one tablet, administered orally in fed state on Day 1 in intervention period 1, the washout between the 2 intervention periods was set to be ≥ 5 days	Participants received single dose of Daprodustat 4mg one tablet, administered orally in fasted state on Day 1 in intervention Period 2
Measure Participants	12	12
PR Interval, Aggregate, 3hours	-6.2 (6.00)	-2.7 (9.55)
PR Interval, Aggregate, 24hours	-4.0 (7.53)	-3.2 (7.11)
QRS Duration, Aggregate, 3hours	-1.5 (4.52)	-0.5 (5.13)
QRS Duration, Aggregate, 24hours	-0.8 (4.39)	2.8 (7.93)
QT interval, Aggregate, 3hours	-13.0 (15.81)	1.0 (16.28)
QT Interval, Aggregate, 24hours	-7.3 (13.73)	-2.2 (12.34)
QTcF Interval, Aggregate, 3hours	-5.3 (11.93)	1.2 (13.64)
QTcF Interval, Aggregate, 24hours	-0.6 (12.87)	-1.1 (9.69)

Adverse Events

Time Frame	AEs and SAEs were collected from the Day -1 up to follow-up ( 16 days for Part 1 and Part 2)
Adverse Event Reporting Description	Safety Population was used. Safety Population comprised of all participants who received at least one dose of a study treatment.
Arm/Group Title	Daprodustat 2mg*2 Followed by Daprodustat 4mg*1		Daprodustat 4mg*1 Tablet Followed by Daprodustat 2mg*2tablets		Daprodustat 4mg*1 (Fed) Followed by Daprodustat 4mg*1 (Fasted)		Daprodustat 4mg*1 (Fasted) Followed by Daprodustat 4mg*1(Fed)
Arm/Group Description	Participants received a single dose Daprodustat 2 milligram (mg) two tablets followed by Daprodustat 4 mg single tablet, administered orally on Day 1.		Participants received a single dose Daprodustat 4 mg one tablet followed by Daprodustat 2 mg two tablets, administered orally on Day 1.		Participants received a single dose Daprodustat 4 mg one tablet in fed state followed by Daprodustat 4 mg one tablet as single dose in fasted state, administered orally on Day 1.		Participants received a single dose Daprodustat 4 mg one tablet in fasted state followed by Daprodustat 4 mg one tablet as single dose in fed state, administered orally on Day 1.
All Cause Mortality
	Daprodustat 2mg*2 Followed by Daprodustat 4mg*1		Daprodustat 4mg*1 Tablet Followed by Daprodustat 2mg*2tablets		Daprodustat 4mg*1 (Fed) Followed by Daprodustat 4mg*1 (Fasted)		Daprodustat 4mg*1 (Fasted) Followed by Daprodustat 4mg*1(Fed)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/51 (0%)		0/52 (0%)		0/12 (0%)		0/12 (0%)
Serious Adverse Events
	Daprodustat 2mg*2 Followed by Daprodustat 4mg*1		Daprodustat 4mg*1 Tablet Followed by Daprodustat 2mg*2tablets		Daprodustat 4mg*1 (Fed) Followed by Daprodustat 4mg*1 (Fasted)		Daprodustat 4mg*1 (Fasted) Followed by Daprodustat 4mg*1(Fed)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/51 (0%)		0/52 (0%)		0/12 (0%)		0/12 (0%)
Other (Not Including Serious) Adverse Events
	Daprodustat 2mg*2 Followed by Daprodustat 4mg*1		Daprodustat 4mg*1 Tablet Followed by Daprodustat 2mg*2tablets		Daprodustat 4mg*1 (Fed) Followed by Daprodustat 4mg*1 (Fasted)		Daprodustat 4mg*1 (Fasted) Followed by Daprodustat 4mg*1(Fed)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/51 (5.9%)		1/52 (1.9%)		0/12 (0%)		0/12 (0%)
Infections and infestations
Tonsilitis	2/51 (3.9%)	2	1/52 (1.9%)	1	0/12 (0%)	0	0/12 (0%)	0
Nasopharyngitis	1/51 (2%)	1	0/52 (0%)	0	0/12 (0%)	0	0/12 (0%)	0
Pharyngitis	0/51 (0%)	0	1/52 (1.9%)	1	0/12 (0%)	0	0/12 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.