Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment Group A: Part 1 | Experimental | Subjects will be randomized to receive single dose of two tablets of 2 mg daprodustat in Period 1 and in Period 2 subjects will receive single dose of 4 mg daprodustat. There will be a wash-out period of 5 days between the Periods. |
|
| Treatment Group B: Part 1 | Experimental | Subjects will be randomized to receive single dose of 4 mg daprodustat in Period 1 and in Period 2 subjects will receive single dose of two tablets of 2 mg daprodustat. There will be a wash-out period of 5 days between the Periods. |
|
| Treatment Group C: Part 2 | Experimental | Subjects will be randomized to receive single dose of 4 mg daprodustat in fed state during Period 1 and in Period 2 subjects will receive single dose of 4 mg daprodustat in fasted state. There will be a wash-out period of 5 days between the Periods. |
|
| Treatment Group D: Part 2 | Experimental | Subjects will be randomized to receive single dose of 4 mg daprodustat in fasted state during period 1 and in Period 2 subjects will receive single dose of 4 mg daprodustat in fed state. There will be a wash-out period of 5 days between the Periods. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Daprodustat 2 mg tablet | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 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 |
| 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. | 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 |
| 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. | 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 |
| 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. | 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 |
| Part 1: Percentage of AUC (0-inf) Obtained by Extrapolation (Percentage AUCex) |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Japanese male subjects who will be overtly healthy as determined by medical evaluation will be included in the study.
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| GSK Clinical Trials | GlaxoSmithKline | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| GSK Investigational Site | Fukuoka | 813-0017 | Japan |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 32250021 | Background | Yamada M, Osamura M, Ogura H, Onoue T, Wakamatsu A, Numachi Y, Caltabiano S, Mahar KM. A Single-Dose, Open-Label, Randomized, Two-Way Crossover Study in Healthy Japanese Participants to Evaluate the Bioequivalence and the Food Effect on the Pharmacokinetics of Daprodustat. Clin Pharmacol Drug Dev. 2020 Nov;9(8):978-984. doi: 10.1002/cpdd.793. Epub 2020 Apr 6. |
Not provided
Not provided
IPD for this study will be made available via the Clinical Study Data Request site.
IPD is available via the Clinical Study Data Request site (click on the link provided below)
Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
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.
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.
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Part 1: Daprodustat 2mg*2+ Daprodustat 4mg*1 | Participants received a single dose Daprodustat 2 milligram (mg) two tablets followed by Daprodustat 4 mg single tablet, administered orally on Day 1.There was a washout period of at least 5 days between the 2 intervention periods. |
| FG001 | Part 1: Daprodustat 4mg*1 + Daprodustat 2mg*2 | Participants received a single dose Daprodustat 4 mg one tablet followed by Daprodustat 2 mg two tablets, administered orally on Day 1. There was a washout period of at least 5 days between the 2 intervention periods. |
| FG002 | Part 2: Daprodustat 4mg*1 (Fed) + Daprodustat 4mg*1 (Fast) | Participants received a single dose Daprodustat 4 mg one tablet in fed state followed by Daprodustat 4 mg one tablet as single dose in fasted state, administered orally on Day 1.There was a washout period of at least 5 days between the 2 treatment periods. |
| FG003 | Part 2: Daprodustat 4mg*1 (Fast) + Daprodustat 4mg*1 (Fed) | Participants received a single dose Daprodustat 4 mg one tablet in fasted state followed by Daprodustat 4 mg one tablet as single dose in fed state, administered orally on Day 1.There was a washout period of at least 5 days between the 2 treatment periods. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Part 1, Intervention Period 1 (2 Days) |
| |||||||||||||
| Part 1, Washout Period (at Least 5 Days) |
| |||||||||||||
| Part 1, Intervention Period 2 (2 Days) |
| |||||||||||||
| Part 2, Intervention Period 1 (2 Days) |
| |||||||||||||
| Part 2, Washout Period (at Least 5 Days) |
| |||||||||||||
| Part 2, Intervention Period 2 (2 Days) |
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| BG001 | Total Participants Part 2 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | PK Population | Posted | Geometric Mean | Geometric Coefficient of Variation | Hour*nanogram/milliliter | 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 |
|
AEs and SAEs were collected from the Day -1 up to follow-up ( 16 days for Part 1 and Part 2)
Safety Population was used. Safety Population comprised of all participants who received at least one dose of a study treatment.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Daprodustat 2mg*2 Followed by Daprodustat 4mg*1 | Participants received a single dose Daprodustat 2 milligram (mg) two tablets followed by Daprodustat 4 mg single tablet, administered orally on Day 1. |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Tonsilitis | Infections and infestations | MedDRA 21.0 | Systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| GSK Response Center | GlaxoSmithKline | 866-435-7343 | GSKClinicalSupportHD@gsk.com |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Mar 12, 2018 | Apr 30, 2019 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jul 10, 2018 | May 23, 2019 | SAP_001.pdf |
Not provided
| ID | Term |
|---|---|
| D000740 | Anemia |
| ID | Term |
|---|---|
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C000599718 | GSK1278863 |
| D013607 | Tablets |
| ID | Term |
|---|---|
| D004304 | Dosage Forms |
| D004364 | Pharmaceutical Preparations |
Not provided
Not provided
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.
Not provided
Not provided
Not provided
Not provided
| Daprodustat 4 mg tablet | Drug | 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. |
|
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. |
| 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 |
| 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. | 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 |
| 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. | 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 |
| 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. | 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 |
| 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. | 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 |
| 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. | 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 |
| 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. | 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 |
| 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. | 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 |
| 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. | 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 |
| 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. | 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 |
| 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. | 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 |
| 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. | 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 |
| Up to Day 16 |
| 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. | Baseline (Day -1), 24hours post-dose |
| 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. | Baseline (Day -1), 24hours post-dose |
| 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. | Baseline (Day -1), 24hours post-dose |
| 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. | Baseline (Day -1), 24hours post-dose |
| 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. | Baseline (Day -1), 24hours post-dose |
| 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. | Baseline (Day -1), 24hours post-dose |
| 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. | Baseline (Day -1), 24hours post-dose |
| 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. | Baseline (Day -1), 24hours post-dose |
| 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. | Baseline (Day -1), 24hours post-dose |
| 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. | Baseline (Day -1), 24hours post-dose |
| 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. | Baseline (Day -1), 24hours post-dose |
| 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. | Baseline (Day -1), 24hours post-dose |
| 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. | Baseline (Day -1), 24hours post-dose |
| 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. | Baseline (Day -1), 24hours post-dose |
| 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. | Baseline (Day -1), 3 and 24 hours (post-dose) |
| 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. | Baseline (Day -1), 3 and 24 hours (post-dose) |
| 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. | Baseline (Day -1), 3 and 24 hours (post-dose) |
| 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. | Baseline (Day -1), 3 and 24 hours (post-dose) |
| 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. | Baseline (Day -1), 3 and 24 hours (post-dose) |
| 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. | Up to Day 16 |
| 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. | Baseline (Day -1), 24 hours (post-dose) |
| 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. | Baseline (Day -1), 24 hours (post-dose) |
| 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. | Baseline (Day -1), 24 hours (post-dose) |
| 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. | Baseline (Day -1), 24 hours (post-dose) |
| 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. | Baseline (Day -1), 24 hours (post-dose) |
| 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. | Baseline (Day -1), 24 hours (post-dose) |
| 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. | Baseline (Day -1), 24 hours (post-dose) |
| 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. | Baseline (Day -1), 24 hours (post-dose) |
| 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. | Baseline (Day -1), 24 hours (post-dose) |
| 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. | Baseline (Day -1), 24 hours (post-dose) |
| 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. | Baseline (Day -1), 24 hours (post-dose) |
| 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. | Baseline (Day -1), 24 hours (post-dose) |
| 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. | Baseline (Day -1), 24 hours (post-dose) |
| 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. | Baseline (Day -1), 24 hours (post-dose) |
| 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. | Baseline (Day -1),3 and 24hours (pre-dose) |
| 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. | Baseline (Day -1),3 and 24hours (pre-dose) |
| 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. | Baseline (Day -1),3 and 24hours (pre-dose) |
| 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. | Baseline (Day -1),3 and 24hours (pre-dose) |
| 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. | Baseline (Day -1),3 and 24hours (pre-dose) |
| COMPLETED |
|
| NOT COMPLETED |
|
|
| COMPLETED |
|
| NOT COMPLETED |
|
| COMPLETED |
|
| NOT COMPLETED |
|
| COMPLETED |
|
| NOT COMPLETED |
|
| COMPLETED |
|
| NOT COMPLETED |
|
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. |
| BG002 | Total | Total of all reporting groups |
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Number | Participants |
|
| OG001 | Part 1: Daprodustat 4mg*1 | Participants received single dose of Daprodustat 4mg one tablet, administered orally in fasted state on Day 1 in either of Period 1 and Period 2 as per randomization schedule |
|
|
|
| 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. | PK Population | Posted | Geometric Mean | Geometric Coefficient of Variation | Nanogram/milliliter | 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 |
|
|
|
|
| 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. | PK Population | Posted | Geometric Mean | Geometric Coefficient of Variation | hour | 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 |
|
|
|
| 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. | PK Population | Posted | Median | Full Range | hour | 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 |
|
|
|
| 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. | PK Population | Posted | Geometric Mean | Geometric Coefficient of Variation | Percentage of 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 |
|
|
|
| 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. | Safety Population | Posted | Geometric Mean | Geometric Coefficient of Variation | Liters per hour | 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 |
|
|
|
| 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. | Safety Population | Posted | Geometric Mean | Geometric Coefficient of Variation | Milliliters (mL) | 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 |
|
|
|
| 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. | Safety Population | Posted | Geometric Mean | Geometric Coefficient of Variation | Per hour | 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 |
|
|
|
| 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. | PK Population | Posted | Geometric Mean | Geometric Coefficient of Variation | Hour*nanogram/milliliter | 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 |
|
|
|
|
| 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. | PK Population | Posted | Geometric Mean | Geometric Coefficient of Variation | Nanogram/milliliter (ng/L) | 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 |
|
|
|
|
| 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. | PK Population | Posted | Geometric Mean | Geometric Coefficient of Variation | hour | 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 |
|
|
|
| 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. | PK Population. | Posted | Median | Full Range | hour | 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 |
|
|
|
| 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. | PK Population. | Posted | Geometric Mean | Geometric Coefficient of Variation | Percentage of 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 |
|
|
|
| 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. | PK Population. | Posted | Geometric Mean | Geometric Coefficient of Variation | Liters per hour | 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 |
|
|
|
| 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. | PK Population. | Posted | Geometric Mean | Geometric Coefficient of Variation | Milliliters (mL) | 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 |
|
|
|
| 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. | PK Population. | Posted | Geometric Mean | Geometric Coefficient of Variation | Per hour | 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 |
|
|
|
| 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. | Safety Population | Posted | Count of Participants | Participants | Up to Day 16 |
|
|
|
| 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. | Safety Population. | Posted | Mean | Standard Deviation | Millimoles per Liter (mmol/L) | Baseline (Day -1), 24hours post-dose |
|
|
|
| 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. | Safety Population. | Posted | Mean | Standard Deviation | International unit per liter (IU/L) | Baseline (Day -1), 24hours post-dose |
|
|
|
| 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. | Safety Population. | Posted | Mean | Standard Deviation | Grams per liter (g/L) | Baseline (Day -1), 24hours post-dose |
|
|
|
| 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. | Safety Population. | Posted | Mean | Standard Deviation | Micromoles per liter (umol/L) | Baseline (Day -1), 24hours post-dose |
|
|
|
| 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. | Safety Population. | Posted | Mean | Standard Deviation | Proportion of red blood cells in blood | Baseline (Day -1), 24hours post-dose |
|
|
|
| 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. | Safety Population. | Posted | Mean | Standard Deviation | Praportion of reticulocytes in blood | Baseline (Day -1), 24hours post-dose |
|
|
|
| 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. | Safety Population. | Posted | Mean | Standard Deviation | Grams per Liter (g/L) | Baseline (Day -1), 24hours post-dose |
|
|
|
| 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. | Safety Population. | Posted | Mean | Standard Deviation | Percentage of cells | Baseline (Day -1), 24hours post-dose |
|
|
|
| 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. | Safety Population. | Posted | Mean | Standard Deviation | Picograms (pg) | Baseline (Day -1), 24hours post-dose |
|
|
|
| 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. | Safety Population. | Posted | Mean | Standard Deviation | Femtoliters | Baseline (Day -1), 24hours post-dose |
|
|
|
| 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. | Safety Population. | Posted | Mean | Standard Deviation | Billion cells per liter (10^9/L) | Baseline (Day -1), 24hours post-dose |
|
|
|
| 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. | Safety Population. | Posted | Mean | Standard Deviation | Trillion cells/liter (10^12 cell/L) | Baseline (Day -1), 24hours post-dose |
|
|
|
| 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. | Safety Population. | Posted | Mean | Standard Deviation | pH | Baseline (Day -1), 24hours post-dose |
|
|
|
| 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. | Safety Population. | Posted | Mean | Standard Deviation | Kilogram per cubic meter | Baseline (Day -1), 24hours post-dose |
|
|
|
| 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. | Safety Population. | Posted | Mean | Standard Deviation | Millimeters of mercury (mmHg) | Baseline (Day -1), 3 and 24 hours (post-dose) |
|
|
|
| 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. | Safety Population. | Posted | Mean | Standard Deviation | Beats per minute | Baseline (Day -1), 3 and 24 hours (post-dose) |
|
|
|
| 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. | Safety Population. | Posted | Mean | Standard Deviation | Celcius (c) | Baseline (Day -1), 3 and 24 hours (post-dose) |
|
|
|
| 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. | Safety Population. | Posted | Mean | Standard Deviation | Beats per minute | Baseline (Day -1), 3 and 24 hours (post-dose) |
|
|
|
| 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. | Safety Population. | Posted | Mean | Standard Deviation | Milliseconds (msec) | Baseline (Day -1), 3 and 24 hours (post-dose) |
|
|
|
| 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. | Safety Population | Posted | Number | Participants | Up to Day 16 |
|
|
|
| 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. | Safety Population | Posted | Mean | Standard Deviation | Millimoles per Liter (mmol/L) | Baseline (Day -1), 24 hours (post-dose) |
|
|
|
| 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. | Safety Population | Posted | Mean | Standard Deviation | International unit per liter (IU/L) | Baseline (Day -1), 24 hours (post-dose) |
|
|
|
| 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. | Safety Population | Posted | Mean | Standard Deviation | Grams per liter (g/L) | Baseline (Day -1), 24 hours (post-dose) |
|
|
|
| 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. | Safety Population | Posted | Mean | Standard Deviation | Micromoles per liter (umol/L) | Baseline (Day -1), 24 hours (post-dose) |
|
|
|
| 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. | Safety Population | Posted | Mean | Standard Deviation | Praportion of red blood cells in blood | Baseline (Day -1), 24 hours (post-dose) |
|
|
|
| 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. | Safety Population | Posted | Mean | Standard Deviation | Praportion of reticulocytes in blood | Baseline (Day -1), 24 hours (post-dose) |
|
|
|
| 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. | Safety Population | Posted | Mean | Standard Deviation | Grams per liter (g/L) | Baseline (Day -1), 24 hours (post-dose) |
|
|
|
| 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. | Safety Population | Posted | Mean | Standard Deviation | Percentage of cells | Baseline (Day -1), 24 hours (post-dose) |
|
|
|
| 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. | Safety Population | Posted | Mean | Standard Deviation | picograms | Baseline (Day -1), 24 hours (post-dose) |
|
|
|
| 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. | Safety Population | Posted | Mean | Standard Deviation | Femtoliters | Baseline (Day -1), 24 hours (post-dose) |
|
|
|
| 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. | Safety Population | Posted | Mean | Standard Deviation | Billion cells per liter (10^9/L) | Baseline (Day -1), 24 hours (post-dose) |
|
|
|
| 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. | Safety Population | Posted | Mean | Standard Deviation | Trillion cells/liter (10^12 cell/L) | Baseline (Day -1), 24 hours (post-dose) |
|
|
|
| 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. | Safety Population | Posted | Mean | Standard Deviation | pH | Baseline (Day -1), 24 hours (post-dose) |
|
|
|
| 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. | Safety Population | Posted | Mean | Standard Deviation | Kilogram per cubic meter | Baseline (Day -1), 24 hours (post-dose) |
|
|
|
| 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. | Safety Population | Posted | Mean | Standard Deviation | Millimeters of mercury (mmHg) | Baseline (Day -1),3 and 24hours (pre-dose) |
|
|
|
| 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. | Safety Population | Posted | Mean | Standard Deviation | Beats per minute | Baseline (Day -1),3 and 24hours (pre-dose) |
|
|
|
| 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. | Safety Population | Posted | Mean | Standard Deviation | celcius | Baseline (Day -1),3 and 24hours (pre-dose) |
|
|
|
| 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. | Safety Population | Posted | Mean | Standard Deviation | Beats/minute | Baseline (Day -1),3 and 24hours (pre-dose) |
|
|
|
| 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. | Safety Population | Posted | Mean | Standard Deviation | Milliseconds (msec) | Baseline (Day -1),3 and 24hours (pre-dose) |
|
|
|
| 0 |
| 51 |
| 0 |
| 51 |
| 3 |
| 51 |
| EG001 | Daprodustat 4mg*1 Tablet Followed by Daprodustat 2mg*2tablets | Participants received a single dose Daprodustat 4 mg one tablet followed by Daprodustat 2 mg two tablets, administered orally on Day 1. | 0 | 52 | 0 | 52 | 1 | 52 |
| EG002 | Daprodustat 4mg*1 (Fed) Followed by Daprodustat 4mg*1 (Fasted) | Participants received a single dose Daprodustat 4 mg one tablet in fed state followed by Daprodustat 4 mg one tablet as single dose in fasted state, administered orally on Day 1. | 0 | 12 | 0 | 12 | 0 | 12 |
| EG003 | Daprodustat 4mg*1 (Fasted) Followed by Daprodustat 4mg*1(Fed) | Participants received a single dose Daprodustat 4 mg one tablet in fasted state followed by Daprodustat 4 mg one tablet as single dose in fed state, administered orally on Day 1. | 0 | 12 | 0 | 12 | 0 | 12 |
| Nasopharyngitis | Infections and infestations | MedDRA 21.0 | Systematic Assessment |
|
| Pharyngitis | Infections and infestations | MedDRA 21.0 | Systematic Assessment |
|
GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
| Ratio of geometric mean |
| 0.91 |
| 2-Sided |
| 90 |
| 0.82 |
| 1.01 |
AUC (0-inf) |
| Equivalence |
If the 90% CI of the ratio of geometric mean doesn't fall within a range of 0.80 to 1.25 i.e., null hypothesis is not rejected the bioequivalence is established if the point estimate falls within a range of 0.90 to 1.11 |
| Cholesterol 24hours |
|
| Chloride 24hours |
|
| HDL cholesterol 24hours |
|
| LDL cholesterol 24hours |
|
| Potassium 24hours |
|
| Phosphate 24hours |
|
| Sodium 24hours |
|
| Triglycerides 24hours |
|
| Urea 24hours |
|
| AST 24hours |
|
| Creatine kinase 24hours |
|
| GGT 24hours |
|
| Lactate dehydrogenase 24hours |
|
| Creatinine 24hours |
|
| Urate 24hours |
|
| Lymphocytes 24hours |
|
| Monocytes 24hours |
|
| Neutrophils 24hours |
|
| SBP 3hours |
|
| SBP 24hours |
|
| QRS Duration, Aggregate 3hours |
|
| QRS Duration, Aggregate 24hours |
|
| QT interval, Aggregate 3hours |
|
| QT interval, Aggregate 24hours |
|
| QTcF interval, Aggregate 3hours |
|
| QtcF Interval, Aggregate 24hours |
|
| Cholesterol, 24hours |
|
| Chloride, 24hours |
|
| HDL cholesterol, 24hours |
|
| LDL cholesterol, 24hours |
|
| Potassium, 24hours |
|
| Phosphate, 24hours |
|
| Sodium, 24hours |
|
| Triglycerides, 24hours |
|
| Urea, 24hours |
|
| AST, 24hours |
|
| Creatine kinase, 24hours |
|
| Lactate dehydrogenase, 24hours |
|
| GGT, 24hours |
|
| Creatinine, 24hours |
|
| Urate, 24hours |
|
| Lymphocytes, 24hours |
|
| Monocytes, 24hours |
|
| Neutrophils, 24hours |
|
| SBP, 3hours |
|
| SBP, 24hours |
|
| QRS Duration, Aggregate, 3hours |
|
| QRS Duration, Aggregate, 24hours |
|
| QT interval, Aggregate, 3hours |
|
| QT Interval, Aggregate, 24hours |
|
| QTcF Interval, Aggregate, 3hours |
|
| QTcF Interval, Aggregate, 24hours |
|