Anaemia
Conditions
Keywords
Japan, Crossover, Daprodustat, Bioequivalence, Pharmacokinetics
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.
Interventions
DRUGDaprodustat 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.
DRUGDaprodustat 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.
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
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.
Eligibility
Sex/Gender
MALE
Age
20 Years to 55 Years
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
Countries
Japan
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 details
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.
Participants by arm
| Arm | Count |
|---|---|
| Total Participants Part 1 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. | 52 |
| Total Participants Part 2 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. | 12 |
| Total | 64 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Part 1, Washout Period (at Least 5 Days) | Withdrawal by Subject | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Total Participants Part 1 | Total Participants Part 2 | Total |
|---|---|---|---|
| Age, Continuous | 27.9 Years STANDARD_DEVIATION 6.91 | 30.0 Years STANDARD_DEVIATION 7.51 | 28.3 Years STANDARD_DEVIATION 7.01 |
| Race/Ethnicity, Customized Asian -Japanese Heritage | 52 Participants | 12 Participants | 64 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 52 Participants | 12 Participants | 64 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 51 | 0 / 52 | 0 / 12 | 0 / 12 |
| other Total, other adverse events | 3 / 51 | 1 / 52 | 0 / 12 | 0 / 12 |
| serious Total, serious adverse events | 0 / 51 | 0 / 52 | 0 / 12 | 0 / 12 |
Outcome results
Primary
Part 1:Apparent Clearance (CL/F) of Daprodustat
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
Population: Safety Population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Daprodustat 2mg*2 | Part 1:Apparent Clearance (CL/F) of Daprodustat | 21.8551 Liters per hour | Geometric Coefficient of Variation 30.7 |
| Part 1: Daprodustat 4mg*1 | Part 1:Apparent Clearance (CL/F) of Daprodustat | 22.2382 Liters per hour | Geometric Coefficient of Variation 30.4 |
Primary
Part 1:Apparent Oral Volume of Distribution (Vz/F) of Daprodustat
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
Population: Safety Population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Daprodustat 2mg*2 | Part 1:Apparent Oral Volume of Distribution (Vz/F) of Daprodustat | 102244.3 Milliliters (mL) | Geometric Coefficient of Variation 33.2 |
| Part 1: Daprodustat 4mg*1 | Part 1:Apparent Oral Volume of Distribution (Vz/F) of Daprodustat | 104522.8 Milliliters (mL) | Geometric Coefficient of Variation 30.8 |
Primary
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
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
Population: PK Population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Daprodustat 2mg*2 | 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 | AUC (0-t) | 182.8420 Hour*nanogram/milliliter | Geometric Coefficient of Variation 30.7 |
| Part 1: Daprodustat 2mg*2 | 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 | AUC (0-inf) | 183.0240 Hour*nanogram/milliliter | Geometric Coefficient of Variation 30.7 |
| Part 1: Daprodustat 4mg*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 | AUC (0-t) | 179.6940 Hour*nanogram/milliliter | Geometric Coefficient of Variation 30.4 |
| Part 1: Daprodustat 4mg*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 | AUC (0-inf) | 179.8710 Hour*nanogram/milliliter | Geometric Coefficient of Variation 30.4 |
90% CI: [0.97, 1.07]
90% CI: [0.97, 1.07]
Primary
Part 1: Elimination Rate Constant (Kel) of Daprodustat
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
Population: Safety Population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Daprodustat 2mg*2 | Part 1: Elimination Rate Constant (Kel) of Daprodustat | 0.2138 Per hour | Geometric Coefficient of Variation 14.9 |
| Part 1: Daprodustat 4mg*1 | Part 1: Elimination Rate Constant (Kel) of Daprodustat | 0.2128 Per hour | Geometric Coefficient of Variation 11.8 |
Primary
Part 1:Maximum Observed Drug Concentration (Cmax) of Daprodustat
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
Population: PK Population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Daprodustat 2mg*2 | Part 1:Maximum Observed Drug Concentration (Cmax) of Daprodustat | 88.8811 Nanogram/milliliter | Geometric Coefficient of Variation 37 |
| Part 1: Daprodustat 4mg*1 | Part 1:Maximum Observed Drug Concentration (Cmax) of Daprodustat | 85.1365 Nanogram/milliliter | Geometric Coefficient of Variation 37 |
90% CI: [0.97, 1.12]
Primary
Part 1: Percentage of AUC (0-inf) Obtained by Extrapolation (Percentage AUCex)
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
Population: PK Population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Daprodustat 2mg*2 | Part 1: Percentage of AUC (0-inf) Obtained by Extrapolation (Percentage AUCex) | 0.0862 Percentage of AUCex | Geometric Coefficient of Variation 53.5 |
| Part 1: Daprodustat 4mg*1 | Part 1: Percentage of AUC (0-inf) Obtained by Extrapolation (Percentage AUCex) | 0.0836 Percentage of AUCex | Geometric Coefficient of Variation 55.3 |
Primary
Part 1:Terminal Phase Half-life (T1/2) of Daprodustat and Mean Residence Time (MRT)
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
Population: PK Population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Daprodustat 2mg*2 | Part 1:Terminal Phase Half-life (T1/2) of Daprodustat and Mean Residence Time (MRT) | t1/2 | 3.2427 hour | Geometric Coefficient of Variation 14.9 |
| Part 1: Daprodustat 2mg*2 | Part 1:Terminal Phase Half-life (T1/2) of Daprodustat and Mean Residence Time (MRT) | MRT | 2.8142 hour | Geometric Coefficient of Variation 25.9 |
| Part 1: Daprodustat 4mg*1 | Part 1:Terminal Phase Half-life (T1/2) of Daprodustat and Mean Residence Time (MRT) | t1/2 | 3.2579 hour | Geometric Coefficient of Variation 11.8 |
| Part 1: Daprodustat 4mg*1 | Part 1:Terminal Phase Half-life (T1/2) of Daprodustat and Mean Residence Time (MRT) | MRT | 2.9637 hour | Geometric Coefficient of Variation 23.2 |
Primary
Part 1: Time of Occurrence of Cmax (Tmax) of Daprodustat
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
Population: PK Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: Daprodustat 2mg*2 | Part 1: Time of Occurrence of Cmax (Tmax) of Daprodustat | 2.000 hour |
| Part 1: Daprodustat 4mg*1 | Part 1: Time of Occurrence of Cmax (Tmax) of Daprodustat | 2.000 hour |
Primary
Part 2:AUC[0-t] andAUC [0-inf] of Daprodustat
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
Population: PK Population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Daprodustat 2mg*2 | Part 2:AUC[0-t] andAUC [0-inf] of Daprodustat | AUC (0-t) | 142.9556 Hour*nanogram/milliliter | Geometric Coefficient of Variation 18 |
| Part 1: Daprodustat 2mg*2 | Part 2:AUC[0-t] andAUC [0-inf] of Daprodustat | AUC (0-inf) | 143.1156 Hour*nanogram/milliliter | Geometric Coefficient of Variation 18 |
| Part 1: Daprodustat 4mg*1 | Part 2:AUC[0-t] andAUC [0-inf] of Daprodustat | AUC (0-t) | 156.4222 Hour*nanogram/milliliter | Geometric Coefficient of Variation 19.3 |
| Part 1: Daprodustat 4mg*1 | Part 2:AUC[0-t] andAUC [0-inf] of Daprodustat | AUC (0-inf) | 156.5481 Hour*nanogram/milliliter | Geometric Coefficient of Variation 19.2 |
90% CI: [0.82, 1.01]
90% CI: [0.82, 1.01]
Primary
Part 2: CL/F of Daprodustat
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
Population: PK Population.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Daprodustat 2mg*2 | Part 2: CL/F of Daprodustat | 27.9494 Liters per hour | Geometric Coefficient of Variation 18 |
| Part 1: Daprodustat 4mg*1 | Part 2: CL/F of Daprodustat | 25.5512 Liters per hour | Geometric Coefficient of Variation 19.2 |
Primary
Part 2: Cmax of Daprodustat
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
Population: PK Population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Daprodustat 2mg*2 | Part 2: Cmax of Daprodustat | 67.8240 Nanogram/milliliter (ng/L) | Geometric Coefficient of Variation 26.7 |
| Part 1: Daprodustat 4mg*1 | Part 2: Cmax of Daprodustat | 76.1944 Nanogram/milliliter (ng/L) | Geometric Coefficient of Variation 29.8 |
90% CI: [0.73, 1.08]
Primary
Part 2: Kel of Daprodustat
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
Population: PK Population.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Daprodustat 2mg*2 | Part 2: Kel of Daprodustat | 0.2155 Per hour | Geometric Coefficient of Variation 9.7 |
| Part 1: Daprodustat 4mg*1 | Part 2: Kel of Daprodustat | 0.2140 Per hour | Geometric Coefficient of Variation 8 |
Primary
Part 2: Percentage AUCex of Dapordustat
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
Population: PK Population.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Daprodustat 2mg*2 | Part 2: Percentage AUCex of Dapordustat | 0.1071 Percentage of AUCex | Geometric Coefficient of Variation 30.9 |
| Part 1: Daprodustat 4mg*1 | Part 2: Percentage AUCex of Dapordustat | 0.0723 Percentage of AUCex | Geometric Coefficient of Variation 47.9 |
Primary
Part 2: T1/2 and MRT of Daprodustat
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
Population: PK Population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Daprodustat 2mg*2 | Part 2: T1/2 and MRT of Daprodustat | t1/2 | 3.2160 hour | Geometric Coefficient of Variation 9.7 |
| Part 1: Daprodustat 2mg*2 | Part 2: T1/2 and MRT of Daprodustat | MRT | 3.2420 hour | Geometric Coefficient of Variation 25.2 |
| Part 1: Daprodustat 4mg*1 | Part 2: T1/2 and MRT of Daprodustat | t1/2 | 3.2389 hour | Geometric Coefficient of Variation 8 |
| Part 1: Daprodustat 4mg*1 | Part 2: T1/2 and MRT of Daprodustat | MRT | 2.6695 hour | Geometric Coefficient of Variation 26.8 |
Primary
Part 2: Tmax of Daprodustat
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
Population: PK Population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: Daprodustat 2mg*2 | Part 2: Tmax of Daprodustat | 2.750 hour |
| Part 1: Daprodustat 4mg*1 | Part 2: Tmax of Daprodustat | 1.750 hour |
Primary
Part 2: Vz/F of Daprodustat
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
Population: PK Population.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Daprodustat 2mg*2 | Part 2: Vz/F of Daprodustat | 129676.9 Milliliters (mL) | Geometric Coefficient of Variation 18.7 |
| Part 1: Daprodustat 4mg*1 | Part 2: Vz/F of Daprodustat | 119394.6 Milliliters (mL) | Geometric Coefficient of Variation 19.7 |
Secondary
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.
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
Population: Safety Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Daprodustat 2mg*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. | Chloride 24hours | 0.9 Millimoles per Liter (mmol/L) | Standard Deviation 1.74 |
| Part 1: Daprodustat 2mg*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. | Potassium 24hours | 0.04 Millimoles per Liter (mmol/L) | Standard Deviation 0.295 |
| Part 1: Daprodustat 2mg*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. | Cholesterol 24hours | -0.043607 Millimoles per Liter (mmol/L) | Standard Deviation 0.3197656 |
| Part 1: Daprodustat 2mg*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. | Phosphate 24hours | -0.102568 Millimoles per Liter (mmol/L) | Standard Deviation 0.1114273 |
| Part 1: Daprodustat 2mg*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. | HDL cholesterol 24hours | -0.128793 Millimoles per Liter (mmol/L) | Standard Deviation 0.1230991 |
| Part 1: Daprodustat 2mg*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. | Sodium 24hours | 0.2 Millimoles per Liter (mmol/L) | Standard Deviation 1.37 |
| Part 1: Daprodustat 2mg*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. | Calcium 24hours | -0.016144 Millimoles per Liter (mmol/L) | Standard Deviation 0.069471 |
| Part 1: Daprodustat 2mg*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. | Triglycerides 24hours | 0.21802 Millimoles per Liter (mmol/L) | Standard Deviation 0.273901 |
| Part 1: Daprodustat 2mg*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. | LDL cholesterol 24hours | 0.022818 Millimoles per Liter (mmol/L) | Standard Deviation 0.2151606 |
| Part 1: Daprodustat 2mg*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. | Urea 24hours | -0.14000 Millimoles per Liter (mmol/L) | Standard Deviation 0.767902 |
| Part 1: Daprodustat 2mg*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. | Glucose 24hours | -0.007619 Millimoles per Liter (mmol/L) | Standard Deviation 0.309469 |
| Part 1: Daprodustat 4mg*1 | 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. | Urea 24hours | -0.29178 Millimoles per Liter (mmol/L) | Standard Deviation 0.84024 |
| Part 1: Daprodustat 4mg*1 | 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. | Glucose 24hours | -0.004270 Millimoles per Liter (mmol/L) | Standard Deviation 0.3243933 |
| Part 1: Daprodustat 4mg*1 | 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. | Calcium 24hours | -0.015834 Millimoles per Liter (mmol/L) | Standard Deviation 0.0623072 |
| Part 1: Daprodustat 4mg*1 | 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. | Cholesterol 24hours | 0.046747 Millimoles per Liter (mmol/L) | Standard Deviation 0.2952955 |
| Part 1: Daprodustat 4mg*1 | 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. | Chloride 24hours | 0.5 Millimoles per Liter (mmol/L) | Standard Deviation 1.63 |
| Part 1: Daprodustat 4mg*1 | 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. | HDL cholesterol 24hours | -0.111397 Millimoles per Liter (mmol/L) | Standard Deviation 0.1067511 |
| Part 1: Daprodustat 4mg*1 | 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. | LDL cholesterol 24hours | 0.099462 Millimoles per Liter (mmol/L) | Standard Deviation 0.2265669 |
| Part 1: Daprodustat 4mg*1 | 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. | Potassium 24hours | 0.03 Millimoles per Liter (mmol/L) | Standard Deviation 0.272 |
| Part 1: Daprodustat 4mg*1 | 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. | Phosphate 24hours | -0.091281 Millimoles per Liter (mmol/L) | Standard Deviation 0.111071 |
| Part 1: Daprodustat 4mg*1 | 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. | Sodium 24hours | 0.0 Millimoles per Liter (mmol/L) | Standard Deviation 1.5 |
| Part 1: Daprodustat 4mg*1 | 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. | Triglycerides 24hours | 0.16385 Millimoles per Liter (mmol/L) | Standard Deviation 0.274955 |
Secondary
Part 1: Change From Baseline in Chemistry Parameters; Albumin, Protein.
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
Population: Safety Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Daprodustat 2mg*2 | Part 1: Change From Baseline in Chemistry Parameters; Albumin, Protein. | Albumin 24hours | -2.0 Grams per liter (g/L) | Standard Deviation 1.74 |
| Part 1: Daprodustat 2mg*2 | Part 1: Change From Baseline in Chemistry Parameters; Albumin, Protein. | Protein 24hours | -2.3 Grams per liter (g/L) | Standard Deviation 2.9 |
| Part 1: Daprodustat 4mg*1 | Part 1: Change From Baseline in Chemistry Parameters; Albumin, Protein. | Albumin 24hours | -2.0 Grams per liter (g/L) | Standard Deviation 1.69 |
| Part 1: Daprodustat 4mg*1 | Part 1: Change From Baseline in Chemistry Parameters; Albumin, Protein. | Protein 24hours | -2.1 Grams per liter (g/L) | Standard Deviation 2.35 |
Secondary
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).
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
Population: Safety Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Daprodustat 2mg*2 | 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). | ALT 24hours | -2.0 International unit per liter (IU/L) | Standard Deviation 3.65 |
| Part 1: Daprodustat 2mg*2 | 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). | Creatine kinase 24hours | -33.9 International unit per liter (IU/L) | Standard Deviation 28.73 |
| Part 1: Daprodustat 2mg*2 | 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). | ALP 24hours | -9.5 International unit per liter (IU/L) | Standard Deviation 17.24 |
| Part 1: Daprodustat 2mg*2 | 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). | GGT 24hours | -1.6 International unit per liter (IU/L) | Standard Deviation 2.34 |
| Part 1: Daprodustat 2mg*2 | 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). | AST 24hours | -2.1 International unit per liter (IU/L) | Standard Deviation 3.19 |
| Part 1: Daprodustat 2mg*2 | 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). | Lactate dehydrogenase 24hours | -20.5 International unit per liter (IU/L) | Standard Deviation 12.3 |
| Part 1: Daprodustat 4mg*1 | 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). | Lactate dehydrogenase 24hours | -19.2 International unit per liter (IU/L) | Standard Deviation 9.15 |
| Part 1: Daprodustat 4mg*1 | 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). | ALP 24hours | -10.8 International unit per liter (IU/L) | Standard Deviation 12.83 |
| Part 1: Daprodustat 4mg*1 | 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). | ALT 24hours | -1.0 International unit per liter (IU/L) | Standard Deviation 3.19 |
| Part 1: Daprodustat 4mg*1 | 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). | AST 24hours | -1.8 International unit per liter (IU/L) | Standard Deviation 3.22 |
| Part 1: Daprodustat 4mg*1 | 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). | Creatine kinase 24hours | -32.3 International unit per liter (IU/L) | Standard Deviation 30.24 |
| Part 1: Daprodustat 4mg*1 | 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). | GGT 24hours | -1.1 International unit per liter (IU/L) | Standard Deviation 1.34 |
Secondary
Part 1: Change From Baseline in Chemistry Parameters; Direct Bilirubin, Bilirubin, Creatinine, Urate
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
Population: Safety Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Daprodustat 2mg*2 | Part 1: Change From Baseline in Chemistry Parameters; Direct Bilirubin, Bilirubin, Creatinine, Urate | Direct bilirubin 24hours | 0.268 Micromoles per liter (umol/L) | Standard Deviation 0.7151 |
| Part 1: Daprodustat 2mg*2 | Part 1: Change From Baseline in Chemistry Parameters; Direct Bilirubin, Bilirubin, Creatinine, Urate | Bilirubin 24hours | 2.615 Micromoles per liter (umol/L) | Standard Deviation 5.0537 |
| Part 1: Daprodustat 2mg*2 | Part 1: Change From Baseline in Chemistry Parameters; Direct Bilirubin, Bilirubin, Creatinine, Urate | Creatinine 24hours | 1.7160 Micromoles per liter (umol/L) | Standard Deviation 4.18539 |
| Part 1: Daprodustat 2mg*2 | Part 1: Change From Baseline in Chemistry Parameters; Direct Bilirubin, Bilirubin, Creatinine, Urate | Urate 24hours | 26.1245 Micromoles per liter (umol/L) | Standard Deviation 28.30344 |
| Part 1: Daprodustat 4mg*1 | Part 1: Change From Baseline in Chemistry Parameters; Direct Bilirubin, Bilirubin, Creatinine, Urate | Urate 24hours | 25.6222 Micromoles per liter (umol/L) | Standard Deviation 28.35581 |
| Part 1: Daprodustat 4mg*1 | Part 1: Change From Baseline in Chemistry Parameters; Direct Bilirubin, Bilirubin, Creatinine, Urate | Direct bilirubin 24hours | 0.164 Micromoles per liter (umol/L) | Standard Deviation 0.6989 |
| Part 1: Daprodustat 4mg*1 | Part 1: Change From Baseline in Chemistry Parameters; Direct Bilirubin, Bilirubin, Creatinine, Urate | Creatinine 24hours | 1.4110 Micromoles per liter (umol/L) | Standard Deviation 4.84901 |
| Part 1: Daprodustat 4mg*1 | Part 1: Change From Baseline in Chemistry Parameters; Direct Bilirubin, Bilirubin, Creatinine, Urate | Bilirubin 24hours | 2.960 Micromoles per liter (umol/L) | Standard Deviation 4.7784 |
Secondary
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
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)
Population: Safety Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Daprodustat 2mg*2 | 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 | QtcF Interval, Aggregate 24hours | -2.4 Milliseconds (msec) | Standard Deviation 13.65 |
| Part 1: Daprodustat 2mg*2 | 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 | QTcF interval, Aggregate 3hours | 1.2 Milliseconds (msec) | Standard Deviation 14.98 |
| Part 1: Daprodustat 2mg*2 | 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 | PR Interval, Aggregate 3hours | -3.3 Milliseconds (msec) | Standard Deviation 10.87 |
| Part 1: Daprodustat 2mg*2 | 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 | PR Interval, Aggregate 24hours | 1.4 Milliseconds (msec) | Standard Deviation 8.13 |
| Part 1: Daprodustat 2mg*2 | 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 | QRS Duration, Aggregate 3hours | -2.8 Milliseconds (msec) | Standard Deviation 6.5 |
| Part 1: Daprodustat 2mg*2 | 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 | QRS Duration, Aggregate 24hours | -1.6 Milliseconds (msec) | Standard Deviation 6.62 |
| Part 1: Daprodustat 2mg*2 | 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 | QT interval, Aggregate 3hours | 0.0 Milliseconds (msec) | Standard Deviation 20.31 |
| Part 1: Daprodustat 2mg*2 | 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 | QT interval, Aggregate 24hours | -5.2 Milliseconds (msec) | Standard Deviation 17.42 |
| Part 1: Daprodustat 4mg*1 | 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 | QT interval, Aggregate 24hours | -5.3 Milliseconds (msec) | Standard Deviation 18.33 |
| Part 1: Daprodustat 4mg*1 | 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 | QRS Duration, Aggregate 3hours | -1.5 Milliseconds (msec) | Standard Deviation 6.42 |
| Part 1: Daprodustat 4mg*1 | 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 | QRS Duration, Aggregate 24hours | 0.2 Milliseconds (msec) | Standard Deviation 6.5 |
| Part 1: Daprodustat 4mg*1 | 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 | QtcF Interval, Aggregate 24hours | -3.1 Milliseconds (msec) | Standard Deviation 13.7 |
| Part 1: Daprodustat 4mg*1 | 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 | QTcF interval, Aggregate 3hours | 1.6 Milliseconds (msec) | Standard Deviation 14.73 |
| Part 1: Daprodustat 4mg*1 | 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 | QT interval, Aggregate 3hours | 0.8 Milliseconds (msec) | Standard Deviation 17.63 |
| Part 1: Daprodustat 4mg*1 | 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 | PR Interval, Aggregate 24hours | 0.0 Milliseconds (msec) | Standard Deviation 12.55 |
| Part 1: Daprodustat 4mg*1 | 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 | PR Interval, Aggregate 3hours | -3.8 Milliseconds (msec) | Standard Deviation 9.4 |
Secondary
Part 1: Change From Baseline in Electrocardiogram (ECG) Parameter; Mean Heart Rate (HR)
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)
Population: Safety Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Daprodustat 2mg*2 | Part 1: Change From Baseline in Electrocardiogram (ECG) Parameter; Mean Heart Rate (HR) | Mean HR 3hours | 0.6 Beats per minute | Standard Deviation 5.01 |
| Part 1: Daprodustat 2mg*2 | Part 1: Change From Baseline in Electrocardiogram (ECG) Parameter; Mean Heart Rate (HR) | Mean HR 24hours | 1.2 Beats per minute | Standard Deviation 4.28 |
| Part 1: Daprodustat 4mg*1 | Part 1: Change From Baseline in Electrocardiogram (ECG) Parameter; Mean Heart Rate (HR) | Mean HR 3hours | 0.2 Beats per minute | Standard Deviation 4.21 |
| Part 1: Daprodustat 4mg*1 | Part 1: Change From Baseline in Electrocardiogram (ECG) Parameter; Mean Heart Rate (HR) | Mean HR 24hours | 0.8 Beats per minute | Standard Deviation 5.18 |
Secondary
Part 1: Change From Baseline in Hematology Parameter Erythrocyte MCHC
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
Population: Safety Population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Daprodustat 2mg*2 | Part 1: Change From Baseline in Hematology Parameter Erythrocyte MCHC | 0.11 Picograms (pg) | Standard Deviation 0.331 |
| Part 1: Daprodustat 4mg*1 | Part 1: Change From Baseline in Hematology Parameter Erythrocyte MCHC | 0.01 Picograms (pg) | Standard Deviation 0.319 |
Secondary
Part 1: Change From Baseline in Hematology Parameter Erythrocyte Mean Corpuscular Volume (EMCV)
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
Population: Safety Population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Daprodustat 2mg*2 | Part 1: Change From Baseline in Hematology Parameter Erythrocyte Mean Corpuscular Volume (EMCV) | -0.2 Femtoliters | Standard Deviation 0.75 |
| Part 1: Daprodustat 4mg*1 | Part 1: Change From Baseline in Hematology Parameter Erythrocyte Mean Corpuscular Volume (EMCV) | -0.2 Femtoliters | Standard Deviation 0.83 |
Secondary
Part 1: Change From Baseline in Hematology Parameter: Erythrocytes
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
Population: Safety Population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Daprodustat 2mg*2 | Part 1: Change From Baseline in Hematology Parameter: Erythrocytes | 0.018 Trillion cells/liter (10^12 cell/L) | Standard Deviation 0.1941 |
| Part 1: Daprodustat 4mg*1 | Part 1: Change From Baseline in Hematology Parameter: Erythrocytes | 0.023 Trillion cells/liter (10^12 cell/L) | Standard Deviation 0.1771 |
Secondary
Part 1:Change From Baseline in Hematology Parameter; Hematocrit
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
Population: Safety Population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Daprodustat 2mg*2 | Part 1:Change From Baseline in Hematology Parameter; Hematocrit | 0.0005 Proportion of red blood cells in blood | Standard Deviation 0.01593 |
| Part 1: Daprodustat 4mg*1 | Part 1:Change From Baseline in Hematology Parameter; Hematocrit | 0.0014 Proportion of red blood cells in blood | Standard Deviation 0.01464 |
Secondary
Part 1:Change From Baseline in Hematology Parameter; Reticulocytes
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
Population: Safety Population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Daprodustat 2mg*2 | Part 1:Change From Baseline in Hematology Parameter; Reticulocytes | -0.0005 Praportion of reticulocytes in blood | Standard Deviation 0.00179 |
| Part 1: Daprodustat 4mg*1 | Part 1:Change From Baseline in Hematology Parameter; Reticulocytes | -0.0001 Praportion of reticulocytes in blood | Standard Deviation 0.00189 |
Secondary
Part 1: Change From Baseline in Hematology Parameters; Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils
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
Population: Safety Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Daprodustat 2mg*2 | Part 1: Change From Baseline in Hematology Parameters; Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils | Eosinophils 24hours | 0.27 Percentage of cells | Standard Deviation 0.871 |
| Part 1: Daprodustat 2mg*2 | Part 1: Change From Baseline in Hematology Parameters; Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils | Monocytes 24hours | -0.43 Percentage of cells | Standard Deviation 1.293 |
| Part 1: Daprodustat 2mg*2 | Part 1: Change From Baseline in Hematology Parameters; Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils | Lymphocytes 24hours | -1.47 Percentage of cells | Standard Deviation 6.07 |
| Part 1: Daprodustat 2mg*2 | Part 1: Change From Baseline in Hematology Parameters; Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils | Neutrophils 24hours | 1.64 Percentage of cells | Standard Deviation 6.407 |
| Part 1: Daprodustat 2mg*2 | Part 1: Change From Baseline in Hematology Parameters; Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils | Basophils 24hours | -0.01 Percentage of cells | Standard Deviation 0.173 |
| Part 1: Daprodustat 4mg*1 | Part 1: Change From Baseline in Hematology Parameters; Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils | Neutrophils 24hours | 0.94 Percentage of cells | Standard Deviation 7.48 |
| Part 1: Daprodustat 4mg*1 | Part 1: Change From Baseline in Hematology Parameters; Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils | Basophils 24hours | 0.00 Percentage of cells | Standard Deviation 0.197 |
| Part 1: Daprodustat 4mg*1 | Part 1: Change From Baseline in Hematology Parameters; Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils | Eosinophils 24hours | 0.25 Percentage of cells | Standard Deviation 0.874 |
| Part 1: Daprodustat 4mg*1 | Part 1: Change From Baseline in Hematology Parameters; Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils | Lymphocytes 24hours | -0.86 Percentage of cells | Standard Deviation 7.049 |
| Part 1: Daprodustat 4mg*1 | Part 1: Change From Baseline in Hematology Parameters; Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils | Monocytes 24hours | -0.33 Percentage of cells | Standard Deviation 1.108 |
Secondary
Part 1: Change From Baseline in Hematology Parameters; Hemoglobin (Hb), Erythrocyte Mean Corpuscular Hb Concentration (MCHC)
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
Population: Safety Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Daprodustat 2mg*2 | Part 1: Change From Baseline in Hematology Parameters; Hemoglobin (Hb), Erythrocyte Mean Corpuscular Hb Concentration (MCHC) | Hb 24hours | 1.1 Grams per Liter (g/L) | Standard Deviation 5.81 |
| Part 1: Daprodustat 2mg*2 | Part 1: Change From Baseline in Hematology Parameters; Hemoglobin (Hb), Erythrocyte Mean Corpuscular Hb Concentration (MCHC) | MCHC 24hours | 2.1 Grams per Liter (g/L) | Standard Deviation 4.23 |
| Part 1: Daprodustat 4mg*1 | Part 1: Change From Baseline in Hematology Parameters; Hemoglobin (Hb), Erythrocyte Mean Corpuscular Hb Concentration (MCHC) | Hb 24hours | 0.8 Grams per Liter (g/L) | Standard Deviation 4.99 |
| Part 1: Daprodustat 4mg*1 | Part 1: Change From Baseline in Hematology Parameters; Hemoglobin (Hb), Erythrocyte Mean Corpuscular Hb Concentration (MCHC) | MCHC 24hours | 0.8 Grams per Liter (g/L) | Standard Deviation 4.99 |
Secondary
Part 1: Change From Baseline in Hematology Parameters Platelets, Leukocytes
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
Population: Safety Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Daprodustat 2mg*2 | Part 1: Change From Baseline in Hematology Parameters Platelets, Leukocytes | Platelets 24hours | 0.7 Billion cells per liter (10^9/L) | Standard Deviation 13.21 |
| Part 1: Daprodustat 2mg*2 | Part 1: Change From Baseline in Hematology Parameters Platelets, Leukocytes | Leukocytes 24hours | -0.55 Billion cells per liter (10^9/L) | Standard Deviation 0.883 |
| Part 1: Daprodustat 4mg*1 | Part 1: Change From Baseline in Hematology Parameters Platelets, Leukocytes | Platelets 24hours | 2.0 Billion cells per liter (10^9/L) | Standard Deviation 14.97 |
| Part 1: Daprodustat 4mg*1 | Part 1: Change From Baseline in Hematology Parameters Platelets, Leukocytes | Leukocytes 24hours | -0.53 Billion cells per liter (10^9/L) | Standard Deviation 0.928 |
Secondary
Part 1: Change From Baseline in Pulse Rate
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)
Population: Safety Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Daprodustat 2mg*2 | Part 1: Change From Baseline in Pulse Rate | Pulse rate 3hours | 0.0 Beats per minute | Standard Deviation 6.91 |
| Part 1: Daprodustat 2mg*2 | Part 1: Change From Baseline in Pulse Rate | Pulse rate 24hours | 0.1 Beats per minute | Standard Deviation 6.04 |
| Part 1: Daprodustat 4mg*1 | Part 1: Change From Baseline in Pulse Rate | Pulse rate 3hours | 0.7 Beats per minute | Standard Deviation 4.78 |
| Part 1: Daprodustat 4mg*1 | Part 1: Change From Baseline in Pulse Rate | Pulse rate 24hours | 1.0 Beats per minute | Standard Deviation 5.12 |
Secondary
Part 1: Change From Baseline in Temperature
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)
Population: Safety Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Daprodustat 2mg*2 | Part 1: Change From Baseline in Temperature | Temperature 3hours | 0.23 Celcius (c) | Standard Deviation 0.256 |
| Part 1: Daprodustat 2mg*2 | Part 1: Change From Baseline in Temperature | Temperature 24hours | 0.10 Celcius (c) | Standard Deviation 0.212 |
| Part 1: Daprodustat 4mg*1 | Part 1: Change From Baseline in Temperature | Temperature 3hours | 0.22 Celcius (c) | Standard Deviation 0.311 |
| Part 1: Daprodustat 4mg*1 | Part 1: Change From Baseline in Temperature | Temperature 24hours | 0.05 Celcius (c) | Standard Deviation 0.33 |
Secondary
Part 1: Change From Baseline in Urinalysis Parameter; Potential of Hydrogen (pH)
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
Population: Safety Population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Daprodustat 2mg*2 | Part 1: Change From Baseline in Urinalysis Parameter; Potential of Hydrogen (pH) | -0.04 pH | Standard Deviation 0.573 |
| Part 1: Daprodustat 4mg*1 | Part 1: Change From Baseline in Urinalysis Parameter; Potential of Hydrogen (pH) | -0.07 pH | Standard Deviation 0.714 |
Secondary
Part 1: Change From Baseline in Urinalysis Parameter; Specific Gravity
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
Population: Safety Population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Daprodustat 2mg*2 | Part 1: Change From Baseline in Urinalysis Parameter; Specific Gravity | 0.0092 Kilogram per cubic meter | Standard Deviation 0.00744 |
| Part 1: Daprodustat 4mg*1 | Part 1: Change From Baseline in Urinalysis Parameter; Specific Gravity | 0.0088 Kilogram per cubic meter | Standard Deviation 0.00767 |
Secondary
Part 1: Change From Baseline in Vital Signs; Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)
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)
Population: Safety Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Daprodustat 2mg*2 | Part 1: Change From Baseline in Vital Signs; Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | DBP 3hours | -2.9 Millimeters of mercury (mmHg) | Standard Deviation 5.84 |
| Part 1: Daprodustat 2mg*2 | Part 1: Change From Baseline in Vital Signs; Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | DBP 24hours | -1.8 Millimeters of mercury (mmHg) | Standard Deviation 6.38 |
| Part 1: Daprodustat 2mg*2 | Part 1: Change From Baseline in Vital Signs; Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | SBP 3hours | -0.6 Millimeters of mercury (mmHg) | Standard Deviation 7.48 |
| Part 1: Daprodustat 2mg*2 | Part 1: Change From Baseline in Vital Signs; Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | SBP 24hours | -0.9 Millimeters of mercury (mmHg) | Standard Deviation 8.07 |
| Part 1: Daprodustat 4mg*1 | Part 1: Change From Baseline in Vital Signs; Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | SBP 24hours | 0.2 Millimeters of mercury (mmHg) | Standard Deviation 8.93 |
| Part 1: Daprodustat 4mg*1 | Part 1: Change From Baseline in Vital Signs; Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | DBP 3hours | -1.5 Millimeters of mercury (mmHg) | Standard Deviation 7 |
| Part 1: Daprodustat 4mg*1 | Part 1: Change From Baseline in Vital Signs; Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | SBP 3hours | -0.4 Millimeters of mercury (mmHg) | Standard Deviation 7.92 |
| Part 1: Daprodustat 4mg*1 | Part 1: Change From Baseline in Vital Signs; Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | DBP 24hours | 0.1 Millimeters of mercury (mmHg) | Standard Deviation 7.67 |
Secondary
Part 1: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
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
Population: Safety Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: Daprodustat 2mg*2 | Part 1: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any SAE | 0 Participants |
| Part 1: Daprodustat 2mg*2 | Part 1: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any AE | 3 Participants |
| Part 1: Daprodustat 4mg*1 | Part 1: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any AE | 1 Participants |
| Part 1: Daprodustat 4mg*1 | Part 1: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any SAE | 0 Participants |
Secondary
Part 2: Change From Baseline Chemistry Parameters; Glucose, Calcium, Cholesterol, Chloride, HDL Cholesterol, LDL Cholesterol, Potassium, Phosphate, Sodium, Triglycerides, and Urea
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)
Population: Safety Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Daprodustat 2mg*2 | Part 2: Change From Baseline Chemistry Parameters; Glucose, Calcium, Cholesterol, Chloride, HDL Cholesterol, LDL Cholesterol, Potassium, Phosphate, Sodium, Triglycerides, and Urea | Chloride, 24hours | 1.5 Millimoles per Liter (mmol/L) | Standard Deviation 1.45 |
| Part 1: Daprodustat 2mg*2 | Part 2: Change From Baseline Chemistry Parameters; Glucose, Calcium, Cholesterol, Chloride, HDL Cholesterol, LDL Cholesterol, Potassium, Phosphate, Sodium, Triglycerides, and Urea | Potassium, 24hours | 0.06 Millimoles per Liter (mmol/L) | Standard Deviation 0.294 |
| Part 1: Daprodustat 2mg*2 | Part 2: Change From Baseline Chemistry Parameters; Glucose, Calcium, Cholesterol, Chloride, HDL Cholesterol, LDL Cholesterol, Potassium, Phosphate, Sodium, Triglycerides, and Urea | Cholesterol, 24hours | -0.172400 Millimoles per Liter (mmol/L) | Standard Deviation 0.2567913 |
| Part 1: Daprodustat 2mg*2 | Part 2: Change From Baseline Chemistry Parameters; Glucose, Calcium, Cholesterol, Chloride, HDL Cholesterol, LDL Cholesterol, Potassium, Phosphate, Sodium, Triglycerides, and Urea | Phosphate, 24hours | -0.029599 Millimoles per Liter (mmol/L) | Standard Deviation 0.0928311 |
| Part 1: Daprodustat 2mg*2 | Part 2: Change From Baseline Chemistry Parameters; Glucose, Calcium, Cholesterol, Chloride, HDL Cholesterol, LDL Cholesterol, Potassium, Phosphate, Sodium, Triglycerides, and Urea | HDL cholesterol, 24hours | -0.165935 Millimoles per Liter (mmol/L) | Standard Deviation 0.099521 |
| Part 1: Daprodustat 2mg*2 | Part 2: Change From Baseline Chemistry Parameters; Glucose, Calcium, Cholesterol, Chloride, HDL Cholesterol, LDL Cholesterol, Potassium, Phosphate, Sodium, Triglycerides, and Urea | Sodium, 24hours | 0.3 Millimoles per Liter (mmol/L) | Standard Deviation 2.35 |
| Part 1: Daprodustat 2mg*2 | Part 2: Change From Baseline Chemistry Parameters; Glucose, Calcium, Cholesterol, Chloride, HDL Cholesterol, LDL Cholesterol, Potassium, Phosphate, Sodium, Triglycerides, and Urea | Glucose, 24hours | -0.425577 Millimoles per Liter (mmol/L) | Standard Deviation 0.2902134 |
| Part 1: Daprodustat 2mg*2 | Part 2: Change From Baseline Chemistry Parameters; Glucose, Calcium, Cholesterol, Chloride, HDL Cholesterol, LDL Cholesterol, Potassium, Phosphate, Sodium, Triglycerides, and Urea | Triglycerides, 24hours | 0.25331 Millimoles per Liter (mmol/L) | Standard Deviation 0.219827 |
| Part 1: Daprodustat 2mg*2 | Part 2: Change From Baseline Chemistry Parameters; Glucose, Calcium, Cholesterol, Chloride, HDL Cholesterol, LDL Cholesterol, Potassium, Phosphate, Sodium, Triglycerides, and Urea | LDL cholesterol, 24hours | -0.170245 Millimoles per Liter (mmol/L) | Standard Deviation 0.1823445 |
| Part 1: Daprodustat 2mg*2 | Part 2: Change From Baseline Chemistry Parameters; Glucose, Calcium, Cholesterol, Chloride, HDL Cholesterol, LDL Cholesterol, Potassium, Phosphate, Sodium, Triglycerides, and Urea | Urea, 24hours | 0.19040 Millimoles per Liter (mmol/L) | Standard Deviation 0.552713 |
| Part 1: Daprodustat 2mg*2 | Part 2: Change From Baseline Chemistry Parameters; Glucose, Calcium, Cholesterol, Chloride, HDL Cholesterol, LDL Cholesterol, Potassium, Phosphate, Sodium, Triglycerides, and Urea | Calcium, 24hours | -0.076929 Millimoles per Liter (mmol/L) | Standard Deviation 0.0515273 |
| Part 1: Daprodustat 4mg*1 | Part 2: Change From Baseline Chemistry Parameters; Glucose, Calcium, Cholesterol, Chloride, HDL Cholesterol, LDL Cholesterol, Potassium, Phosphate, Sodium, Triglycerides, and Urea | Urea, 24hours | -0.14875 Millimoles per Liter (mmol/L) | Standard Deviation 0.588353 |
| Part 1: Daprodustat 4mg*1 | Part 2: Change From Baseline Chemistry Parameters; Glucose, Calcium, Cholesterol, Chloride, HDL Cholesterol, LDL Cholesterol, Potassium, Phosphate, Sodium, Triglycerides, and Urea | Glucose, 24hours | -0.018503 Millimoles per Liter (mmol/L) | Standard Deviation 0.2530908 |
| Part 1: Daprodustat 4mg*1 | Part 2: Change From Baseline Chemistry Parameters; Glucose, Calcium, Cholesterol, Chloride, HDL Cholesterol, LDL Cholesterol, Potassium, Phosphate, Sodium, Triglycerides, and Urea | Calcium, 24hours | -0.058217 Millimoles per Liter (mmol/L) | Standard Deviation 0.0595515 |
| Part 1: Daprodustat 4mg*1 | Part 2: Change From Baseline Chemistry Parameters; Glucose, Calcium, Cholesterol, Chloride, HDL Cholesterol, LDL Cholesterol, Potassium, Phosphate, Sodium, Triglycerides, and Urea | Cholesterol, 24hours | -0.094820 Millimoles per Liter (mmol/L) | Standard Deviation 0.2225472 |
| Part 1: Daprodustat 4mg*1 | Part 2: Change From Baseline Chemistry Parameters; Glucose, Calcium, Cholesterol, Chloride, HDL Cholesterol, LDL Cholesterol, Potassium, Phosphate, Sodium, Triglycerides, and Urea | Chloride, 24hours | 2.1 Millimoles per Liter (mmol/L) | Standard Deviation 2.27 |
| Part 1: Daprodustat 4mg*1 | Part 2: Change From Baseline Chemistry Parameters; Glucose, Calcium, Cholesterol, Chloride, HDL Cholesterol, LDL Cholesterol, Potassium, Phosphate, Sodium, Triglycerides, and Urea | HDL cholesterol, 24hours | -0.148695 Millimoles per Liter (mmol/L) | Standard Deviation 0.0826086 |
| Part 1: Daprodustat 4mg*1 | Part 2: Change From Baseline Chemistry Parameters; Glucose, Calcium, Cholesterol, Chloride, HDL Cholesterol, LDL Cholesterol, Potassium, Phosphate, Sodium, Triglycerides, and Urea | LDL cholesterol, 24hours | -0.066805 Millimoles per Liter (mmol/L) | Standard Deviation 0.1724049 |
| Part 1: Daprodustat 4mg*1 | Part 2: Change From Baseline Chemistry Parameters; Glucose, Calcium, Cholesterol, Chloride, HDL Cholesterol, LDL Cholesterol, Potassium, Phosphate, Sodium, Triglycerides, and Urea | Potassium, 24hours | 0.19 Millimoles per Liter (mmol/L) | Standard Deviation 0.231 |
| Part 1: Daprodustat 4mg*1 | Part 2: Change From Baseline Chemistry Parameters; Glucose, Calcium, Cholesterol, Chloride, HDL Cholesterol, LDL Cholesterol, Potassium, Phosphate, Sodium, Triglycerides, and Urea | Phosphate, 24hours | -0.080725 Millimoles per Liter (mmol/L) | Standard Deviation 0.1324212 |
| Part 1: Daprodustat 4mg*1 | Part 2: Change From Baseline Chemistry Parameters; Glucose, Calcium, Cholesterol, Chloride, HDL Cholesterol, LDL Cholesterol, Potassium, Phosphate, Sodium, Triglycerides, and Urea | Sodium, 24hours | 0.9 Millimoles per Liter (mmol/L) | Standard Deviation 1.38 |
| Part 1: Daprodustat 4mg*1 | Part 2: Change From Baseline Chemistry Parameters; Glucose, Calcium, Cholesterol, Chloride, HDL Cholesterol, LDL Cholesterol, Potassium, Phosphate, Sodium, Triglycerides, and Urea | Triglycerides, 24hours | 0.08475 Millimoles per Liter (mmol/L) | Standard Deviation 0.197228 |
Secondary
Part 2: Change From Baseline in Chemistry Parameters; Albumin, Protein
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)
Population: Safety Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Daprodustat 2mg*2 | Part 2: Change From Baseline in Chemistry Parameters; Albumin, Protein | Albumin 24hours | -3.2 Grams per liter (g/L) | Standard Deviation 1.34 |
| Part 1: Daprodustat 2mg*2 | Part 2: Change From Baseline in Chemistry Parameters; Albumin, Protein | Protein 24hours | -3.4 Grams per liter (g/L) | Standard Deviation 2.94 |
| Part 1: Daprodustat 4mg*1 | Part 2: Change From Baseline in Chemistry Parameters; Albumin, Protein | Albumin 24hours | -1.9 Grams per liter (g/L) | Standard Deviation 1.16 |
| Part 1: Daprodustat 4mg*1 | Part 2: Change From Baseline in Chemistry Parameters; Albumin, Protein | Protein 24hours | -2.6 Grams per liter (g/L) | Standard Deviation 2.02 |
Secondary
Part 2: Change From Baseline in Chemistry Parameters; Direct Bilirubin, Bilirubin, Creatinine, Urate
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)
Population: Safety Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Daprodustat 2mg*2 | Part 2: Change From Baseline in Chemistry Parameters; Direct Bilirubin, Bilirubin, Creatinine, Urate | Direct bilirubin, 24hours | 0.000 Micromoles per liter (umol/L) | Standard Deviation 0 |
| Part 1: Daprodustat 2mg*2 | Part 2: Change From Baseline in Chemistry Parameters; Direct Bilirubin, Bilirubin, Creatinine, Urate | Creatinine, 24hours | -1.6207 Micromoles per liter (umol/L) | Standard Deviation 5.16603 |
| Part 1: Daprodustat 2mg*2 | Part 2: Change From Baseline in Chemistry Parameters; Direct Bilirubin, Bilirubin, Creatinine, Urate | Bilirubin, 24hours | 2.280 Micromoles per liter (umol/L) | Standard Deviation 5.2748 |
| Part 1: Daprodustat 2mg*2 | Part 2: Change From Baseline in Chemistry Parameters; Direct Bilirubin, Bilirubin, Creatinine, Urate | Urate, 24hours | 23.2963 Micromoles per liter (umol/L) | Standard Deviation 20.9847 |
| Part 1: Daprodustat 4mg*1 | Part 2: Change From Baseline in Chemistry Parameters; Direct Bilirubin, Bilirubin, Creatinine, Urate | Urate, 24hours | 21.8093 Micromoles per liter (umol/L) | Standard Deviation 19.53615 |
| Part 1: Daprodustat 4mg*1 | Part 2: Change From Baseline in Chemistry Parameters; Direct Bilirubin, Bilirubin, Creatinine, Urate | Direct bilirubin, 24hours | 0.000 Micromoles per liter (umol/L) | Standard Deviation 1.0312 |
| Part 1: Daprodustat 4mg*1 | Part 2: Change From Baseline in Chemistry Parameters; Direct Bilirubin, Bilirubin, Creatinine, Urate | Bilirubin, 24hours | 1.425 Micromoles per liter (umol/L) | Standard Deviation 3.1643 |
| Part 1: Daprodustat 4mg*1 | Part 2: Change From Baseline in Chemistry Parameters; Direct Bilirubin, Bilirubin, Creatinine, Urate | Creatinine, 24hours | -1.1050 Micromoles per liter (umol/L) | Standard Deviation 5.68072 |
Secondary
Part 2: Change From Baseline in Chemistry Paremeters; ALP, ALT, AST, Creatine Kinase, Lactate Dehydrogenase, GGT
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)
Population: Safety Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Daprodustat 2mg*2 | Part 2: Change From Baseline in Chemistry Paremeters; ALP, ALT, AST, Creatine Kinase, Lactate Dehydrogenase, GGT | ALP, 24hours | -18.9 International unit per liter (IU/L) | Standard Deviation 15.48 |
| Part 1: Daprodustat 2mg*2 | Part 2: Change From Baseline in Chemistry Paremeters; ALP, ALT, AST, Creatine Kinase, Lactate Dehydrogenase, GGT | ALT, 24hours | -3.1 International unit per liter (IU/L) | Standard Deviation 2.43 |
| Part 1: Daprodustat 2mg*2 | Part 2: Change From Baseline in Chemistry Paremeters; ALP, ALT, AST, Creatine Kinase, Lactate Dehydrogenase, GGT | AST, 24hours | -2.8 International unit per liter (IU/L) | Standard Deviation 2.18 |
| Part 1: Daprodustat 2mg*2 | Part 2: Change From Baseline in Chemistry Paremeters; ALP, ALT, AST, Creatine Kinase, Lactate Dehydrogenase, GGT | Creatine kinase, 24hours | -28.3 International unit per liter (IU/L) | Standard Deviation 13.7 |
| Part 1: Daprodustat 2mg*2 | Part 2: Change From Baseline in Chemistry Paremeters; ALP, ALT, AST, Creatine Kinase, Lactate Dehydrogenase, GGT | Lactate dehydrogenase, 24hours | -21.0 International unit per liter (IU/L) | Standard Deviation 9.68 |
| Part 1: Daprodustat 2mg*2 | Part 2: Change From Baseline in Chemistry Paremeters; ALP, ALT, AST, Creatine Kinase, Lactate Dehydrogenase, GGT | GGT, 24hours | -1.0 International unit per liter (IU/L) | Standard Deviation 1.41 |
| Part 1: Daprodustat 4mg*1 | Part 2: Change From Baseline in Chemistry Paremeters; ALP, ALT, AST, Creatine Kinase, Lactate Dehydrogenase, GGT | Lactate dehydrogenase, 24hours | -18.4 International unit per liter (IU/L) | Standard Deviation 9.05 |
| Part 1: Daprodustat 4mg*1 | Part 2: Change From Baseline in Chemistry Paremeters; ALP, ALT, AST, Creatine Kinase, Lactate Dehydrogenase, GGT | ALP, 24hours | -13.3 International unit per liter (IU/L) | Standard Deviation 10.54 |
| Part 1: Daprodustat 4mg*1 | Part 2: Change From Baseline in Chemistry Paremeters; ALP, ALT, AST, Creatine Kinase, Lactate Dehydrogenase, GGT | Creatine kinase, 24hours | -15.3 International unit per liter (IU/L) | Standard Deviation 17.56 |
| Part 1: Daprodustat 4mg*1 | Part 2: Change From Baseline in Chemistry Paremeters; ALP, ALT, AST, Creatine Kinase, Lactate Dehydrogenase, GGT | ALT, 24hours | -3.5 International unit per liter (IU/L) | Standard Deviation 2.02 |
| Part 1: Daprodustat 4mg*1 | Part 2: Change From Baseline in Chemistry Paremeters; ALP, ALT, AST, Creatine Kinase, Lactate Dehydrogenase, GGT | GGT, 24hours | -1.6 International unit per liter (IU/L) | Standard Deviation 2.11 |
| Part 1: Daprodustat 4mg*1 | Part 2: Change From Baseline in Chemistry Paremeters; ALP, ALT, AST, Creatine Kinase, Lactate Dehydrogenase, GGT | AST, 24hours | -2.7 International unit per liter (IU/L) | Standard Deviation 2.46 |
Secondary
Part 2: Change From Baseline in ECG Parameter; Mean Heart Rate (HR)
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)
Population: Safety Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Daprodustat 2mg*2 | Part 2: Change From Baseline in ECG Parameter; Mean Heart Rate (HR) | Mean HR, 3hours | 3.7 Beats/minute | Standard Deviation 6.18 |
| Part 1: Daprodustat 2mg*2 | Part 2: Change From Baseline in ECG Parameter; Mean Heart Rate (HR) | Mean HR, 24hours | 3.1 Beats/minute | Standard Deviation 6.6 |
| Part 1: Daprodustat 4mg*1 | Part 2: Change From Baseline in ECG Parameter; Mean Heart Rate (HR) | Mean HR, 3hours | 0.0 Beats/minute | Standard Deviation 4.07 |
| Part 1: Daprodustat 4mg*1 | Part 2: Change From Baseline in ECG Parameter; Mean Heart Rate (HR) | Mean HR, 24hours | 0.6 Beats/minute | Standard Deviation 4.72 |
Secondary
Part 2: Change From Baseline in ECG Parameter; PR Interval, QRS Interval, QT Interval, QTcF Interval
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)
Population: Safety Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Daprodustat 2mg*2 | Part 2: Change From Baseline in ECG Parameter; PR Interval, QRS Interval, QT Interval, QTcF Interval | PR Interval, Aggregate, 3hours | -6.2 Milliseconds (msec) | Standard Deviation 6 |
| Part 1: Daprodustat 2mg*2 | Part 2: Change From Baseline in ECG Parameter; PR Interval, QRS Interval, QT Interval, QTcF Interval | QT interval, Aggregate, 3hours | -13.0 Milliseconds (msec) | Standard Deviation 15.81 |
| Part 1: Daprodustat 2mg*2 | Part 2: Change From Baseline in ECG Parameter; PR Interval, QRS Interval, QT Interval, QTcF Interval | QRS Duration, Aggregate, 3hours | -1.5 Milliseconds (msec) | Standard Deviation 4.52 |
| Part 1: Daprodustat 2mg*2 | Part 2: Change From Baseline in ECG Parameter; PR Interval, QRS Interval, QT Interval, QTcF Interval | QT Interval, Aggregate, 24hours | -7.3 Milliseconds (msec) | Standard Deviation 13.73 |
| Part 1: Daprodustat 2mg*2 | Part 2: Change From Baseline in ECG Parameter; PR Interval, QRS Interval, QT Interval, QTcF Interval | PR Interval, Aggregate, 24hours | -4.0 Milliseconds (msec) | Standard Deviation 7.53 |
| Part 1: Daprodustat 2mg*2 | Part 2: Change From Baseline in ECG Parameter; PR Interval, QRS Interval, QT Interval, QTcF Interval | QTcF Interval, Aggregate, 3hours | -5.3 Milliseconds (msec) | Standard Deviation 11.93 |
| Part 1: Daprodustat 2mg*2 | Part 2: Change From Baseline in ECG Parameter; PR Interval, QRS Interval, QT Interval, QTcF Interval | QTcF Interval, Aggregate, 24hours | -0.6 Milliseconds (msec) | Standard Deviation 12.87 |
| Part 1: Daprodustat 2mg*2 | Part 2: Change From Baseline in ECG Parameter; PR Interval, QRS Interval, QT Interval, QTcF Interval | QRS Duration, Aggregate, 24hours | -0.8 Milliseconds (msec) | Standard Deviation 4.39 |
| Part 1: Daprodustat 4mg*1 | Part 2: Change From Baseline in ECG Parameter; PR Interval, QRS Interval, QT Interval, QTcF Interval | QTcF Interval, Aggregate, 24hours | -1.1 Milliseconds (msec) | Standard Deviation 9.69 |
| Part 1: Daprodustat 4mg*1 | Part 2: Change From Baseline in ECG Parameter; PR Interval, QRS Interval, QT Interval, QTcF Interval | PR Interval, Aggregate, 3hours | -2.7 Milliseconds (msec) | Standard Deviation 9.55 |
| Part 1: Daprodustat 4mg*1 | Part 2: Change From Baseline in ECG Parameter; PR Interval, QRS Interval, QT Interval, QTcF Interval | PR Interval, Aggregate, 24hours | -3.2 Milliseconds (msec) | Standard Deviation 7.11 |
| Part 1: Daprodustat 4mg*1 | Part 2: Change From Baseline in ECG Parameter; PR Interval, QRS Interval, QT Interval, QTcF Interval | QRS Duration, Aggregate, 3hours | -0.5 Milliseconds (msec) | Standard Deviation 5.13 |
| Part 1: Daprodustat 4mg*1 | Part 2: Change From Baseline in ECG Parameter; PR Interval, QRS Interval, QT Interval, QTcF Interval | QRS Duration, Aggregate, 24hours | 2.8 Milliseconds (msec) | Standard Deviation 7.93 |
| Part 1: Daprodustat 4mg*1 | Part 2: Change From Baseline in ECG Parameter; PR Interval, QRS Interval, QT Interval, QTcF Interval | QT interval, Aggregate, 3hours | 1.0 Milliseconds (msec) | Standard Deviation 16.28 |
| Part 1: Daprodustat 4mg*1 | Part 2: Change From Baseline in ECG Parameter; PR Interval, QRS Interval, QT Interval, QTcF Interval | QT Interval, Aggregate, 24hours | -2.2 Milliseconds (msec) | Standard Deviation 12.34 |
| Part 1: Daprodustat 4mg*1 | Part 2: Change From Baseline in ECG Parameter; PR Interval, QRS Interval, QT Interval, QTcF Interval | QTcF Interval, Aggregate, 3hours | 1.2 Milliseconds (msec) | Standard Deviation 13.64 |
Secondary
Part 2: Change From Baseline in Hematology Parameter: EMCH
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)
Population: Safety Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Daprodustat 2mg*2 | Part 2: Change From Baseline in Hematology Parameter: EMCH | 0.10 picograms | Standard Deviation 0.413 |
| Part 1: Daprodustat 4mg*1 | Part 2: Change From Baseline in Hematology Parameter: EMCH | 0.03 picograms | Standard Deviation 0.311 |
Secondary
Part 2: Change From Baseline in Hematology Parameter EMCV
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)
Population: Safety Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Daprodustat 2mg*2 | Part 2: Change From Baseline in Hematology Parameter EMCV | 0.5 Femtoliters | Standard Deviation 0.67 |
| Part 1: Daprodustat 4mg*1 | Part 2: Change From Baseline in Hematology Parameter EMCV | 0.3 Femtoliters | Standard Deviation 0.97 |
Secondary
Part 2: Change From Baseline in Hematology Parameter Erythrocytes
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)
Population: Safety Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Daprodustat 2mg*2 | Part 2: Change From Baseline in Hematology Parameter Erythrocytes | -0.083 Trillion cells/liter (10^12 cell/L) | Standard Deviation 0.1859 |
| Part 1: Daprodustat 4mg*1 | Part 2: Change From Baseline in Hematology Parameter Erythrocytes | -0.044 Trillion cells/liter (10^12 cell/L) | Standard Deviation 0.1767 |
Secondary
Part 2: Change From Baseline in Hematology Parameters; Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils
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)
Population: Safety Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Daprodustat 2mg*2 | Part 2: Change From Baseline in Hematology Parameters; Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils | Basophils, 24hours | -0.04 Percentage of cells | Standard Deviation 0.193 |
| Part 1: Daprodustat 2mg*2 | Part 2: Change From Baseline in Hematology Parameters; Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils | Lymphocytes, 24hours | -2.31 Percentage of cells | Standard Deviation 3.815 |
| Part 1: Daprodustat 2mg*2 | Part 2: Change From Baseline in Hematology Parameters; Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils | Eosinophils, 24hours | 0.62 Percentage of cells | Standard Deviation 1.62 |
| Part 1: Daprodustat 2mg*2 | Part 2: Change From Baseline in Hematology Parameters; Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils | Monocytes, 24hours | -0.38 Percentage of cells | Standard Deviation 0.732 |
| Part 1: Daprodustat 2mg*2 | Part 2: Change From Baseline in Hematology Parameters; Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils | Neutrophils, 24hours | 2.12 Percentage of cells | Standard Deviation 5.072 |
| Part 1: Daprodustat 4mg*1 | Part 2: Change From Baseline in Hematology Parameters; Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils | Monocytes, 24hours | -0.03 Percentage of cells | Standard Deviation 1.414 |
| Part 1: Daprodustat 4mg*1 | Part 2: Change From Baseline in Hematology Parameters; Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils | Neutrophils, 24hours | 1.83 Percentage of cells | Standard Deviation 5.829 |
| Part 1: Daprodustat 4mg*1 | Part 2: Change From Baseline in Hematology Parameters; Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils | Basophils, 24hours | -0.17 Percentage of cells | Standard Deviation 0.239 |
| Part 1: Daprodustat 4mg*1 | Part 2: Change From Baseline in Hematology Parameters; Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils | Eosinophils, 24hours | -0.49 Percentage of cells | Standard Deviation 0.312 |
| Part 1: Daprodustat 4mg*1 | Part 2: Change From Baseline in Hematology Parameters; Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils | Lymphocytes, 24hours | -1.14 Percentage of cells | Standard Deviation 6.015 |
Secondary
Part 2: Change From Baseline in Hematology Parameters; Hb, Erythrocyte MCHC
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)
Population: Safety Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Daprodustat 2mg*2 | Part 2: Change From Baseline in Hematology Parameters; Hb, Erythrocyte MCHC | Hb 24hours | -2.1 Grams per liter (g/L) | Standard Deviation 5.28 |
| Part 1: Daprodustat 2mg*2 | Part 2: Change From Baseline in Hematology Parameters; Hb, Erythrocyte MCHC | EMCH concentration 24hours | 0.4 Grams per liter (g/L) | Standard Deviation 5.55 |
| Part 1: Daprodustat 4mg*1 | Part 2: Change From Baseline in Hematology Parameters; Hb, Erythrocyte MCHC | Hb 24hours | -1.2 Grams per liter (g/L) | Standard Deviation 5.37 |
| Part 1: Daprodustat 4mg*1 | Part 2: Change From Baseline in Hematology Parameters; Hb, Erythrocyte MCHC | EMCH concentration 24hours | -0.6 Grams per liter (g/L) | Standard Deviation 4.66 |
Secondary
Part 2: Change From Baseline in Hematology Parameters; Hematocrit
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)
Population: Safety Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Daprodustat 2mg*2 | Part 2: Change From Baseline in Hematology Parameters; Hematocrit | -0.0052 Praportion of red blood cells in blood | Standard Deviation 0.01629 |
| Part 1: Daprodustat 4mg*1 | Part 2: Change From Baseline in Hematology Parameters; Hematocrit | -0.0025 Praportion of red blood cells in blood | Standard Deviation 0.01519 |
Secondary
Part 2: Change From Baseline in Hematology Parameters Platelets, Leukocytes
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)
Population: Safety Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Daprodustat 2mg*2 | Part 2: Change From Baseline in Hematology Parameters Platelets, Leukocytes | Platelets, 24hours | -10.9 Billion cells per liter (10^9/L) | Standard Deviation 11.19 |
| Part 1: Daprodustat 2mg*2 | Part 2: Change From Baseline in Hematology Parameters Platelets, Leukocytes | Leukocytes, 24hours | -0.27 Billion cells per liter (10^9/L) | Standard Deviation 0.78 |
| Part 1: Daprodustat 4mg*1 | Part 2: Change From Baseline in Hematology Parameters Platelets, Leukocytes | Platelets, 24hours | -3.2 Billion cells per liter (10^9/L) | Standard Deviation 12.04 |
| Part 1: Daprodustat 4mg*1 | Part 2: Change From Baseline in Hematology Parameters Platelets, Leukocytes | Leukocytes, 24hours | -0.39 Billion cells per liter (10^9/L) | Standard Deviation 0.579 |
Secondary
Part 2: Change From Baseline in Hematology Parameters; Reticulocytes
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)
Population: Safety Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Daprodustat 2mg*2 | Part 2: Change From Baseline in Hematology Parameters; Reticulocytes | -0.0002 Praportion of reticulocytes in blood | Standard Deviation 0.00164 |
| Part 1: Daprodustat 4mg*1 | Part 2: Change From Baseline in Hematology Parameters; Reticulocytes | -0.0010 Praportion of reticulocytes in blood | Standard Deviation 0.00186 |
Secondary
Part 2: Change From Baseline in Pulse Rate
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)
Population: Safety Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Daprodustat 2mg*2 | Part 2: Change From Baseline in Pulse Rate | Pulse rate, 3hours | 6.1 Beats per minute | Standard Deviation 5.37 |
| Part 1: Daprodustat 2mg*2 | Part 2: Change From Baseline in Pulse Rate | Pulse rate, 24hours | 4.0 Beats per minute | Standard Deviation 5.24 |
| Part 1: Daprodustat 4mg*1 | Part 2: Change From Baseline in Pulse Rate | Pulse rate, 3hours | -1.5 Beats per minute | Standard Deviation 5.82 |
| Part 1: Daprodustat 4mg*1 | Part 2: Change From Baseline in Pulse Rate | Pulse rate, 24hours | 2.9 Beats per minute | Standard Deviation 6.05 |
Secondary
Part 2: Change From Baseline in Temperature
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)
Population: Safety Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Daprodustat 2mg*2 | Part 2: Change From Baseline in Temperature | Temperature, 3hours | 0.28 celcius | Standard Deviation 0.302 |
| Part 1: Daprodustat 2mg*2 | Part 2: Change From Baseline in Temperature | Temperature, 24hours | 0.02 celcius | Standard Deviation 0.424 |
| Part 1: Daprodustat 4mg*1 | Part 2: Change From Baseline in Temperature | Temperature, 3hours | 0.13 celcius | Standard Deviation 0.293 |
| Part 1: Daprodustat 4mg*1 | Part 2: Change From Baseline in Temperature | Temperature, 24hours | 0.03 celcius | Standard Deviation 0.245 |
Secondary
Part 2: Change From Baseline in Urinalysis Parameter; Potential of Hydrogen (pH)
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)
Population: Safety Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Daprodustat 2mg*2 | Part 2: Change From Baseline in Urinalysis Parameter; Potential of Hydrogen (pH) | 0.13 pH | Standard Deviation 0.433 |
| Part 1: Daprodustat 4mg*1 | Part 2: Change From Baseline in Urinalysis Parameter; Potential of Hydrogen (pH) | 0.13 pH | Standard Deviation 0.608 |
Secondary
Part 2: Change From Baseline in Urinalysis Parameter; Specific Gravity
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)
Population: Safety Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Daprodustat 2mg*2 | Part 2: Change From Baseline in Urinalysis Parameter; Specific Gravity | 0.0054 Kilogram per cubic meter | Standard Deviation 0.01215 |
| Part 1: Daprodustat 4mg*1 | Part 2: Change From Baseline in Urinalysis Parameter; Specific Gravity | 0.0013 Kilogram per cubic meter | Standard Deviation 0.009 |
Secondary
Part 2: Change From Baseline in Vital Signs; Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)
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)
Population: Safety Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Daprodustat 2mg*2 | Part 2: Change From Baseline in Vital Signs; Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | DBP, 24hours | -0.6 Millimeters of mercury (mmHg) | Standard Deviation 7.14 |
| Part 1: Daprodustat 2mg*2 | Part 2: Change From Baseline in Vital Signs; Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | DBP, 3hours | -4.8 Millimeters of mercury (mmHg) | Standard Deviation 4.9 |
| Part 1: Daprodustat 2mg*2 | Part 2: Change From Baseline in Vital Signs; Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | SBP, 24hours | 1.4 Millimeters of mercury (mmHg) | Standard Deviation 6.93 |
| Part 1: Daprodustat 2mg*2 | Part 2: Change From Baseline in Vital Signs; Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | SBP, 3hours | 0.7 Millimeters of mercury (mmHg) | Standard Deviation 6.1 |
| Part 1: Daprodustat 4mg*1 | Part 2: Change From Baseline in Vital Signs; Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | SBP, 24hours | 1.3 Millimeters of mercury (mmHg) | Standard Deviation 5.18 |
| Part 1: Daprodustat 4mg*1 | Part 2: Change From Baseline in Vital Signs; Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | DBP, 3hours | 0.2 Millimeters of mercury (mmHg) | Standard Deviation 5.61 |
| Part 1: Daprodustat 4mg*1 | Part 2: Change From Baseline in Vital Signs; Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | SBP, 3hours | -1.3 Millimeters of mercury (mmHg) | Standard Deviation 8.41 |
| Part 1: Daprodustat 4mg*1 | Part 2: Change From Baseline in Vital Signs; Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | DBP, 24hours | 2.8 Millimeters of mercury (mmHg) | Standard Deviation 6.97 |
Secondary
Part 2: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
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
Population: Safety Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part 1: Daprodustat 2mg*2 | Part 2: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any AE | 0 Participants |
| Part 1: Daprodustat 2mg*2 | Part 2: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any SAE | 0 Participants |
| Part 1: Daprodustat 4mg*1 | Part 2: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any SAE | 0 Participants |
| Part 1: Daprodustat 4mg*1 | Part 2: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any AE | 0 Participants |