Anemia Studies in CKD: Erythropoiesis Via a Novel PHI Daprodustat - Pediatric (ASCEND-P)

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. SAEs are defined as any untoward medical occurrence that, at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; or other situations as per medical and scientific judgement of the Investigator.

AESIs are AEs of scientific interest specific to the drug class as per investigator assessment. AESI included: Death, Myocardial Infarction (MI), stroke, Heart Failure (HF), thromboembolic events, thrombosis of vascular access, Thrombosis and/or tissue ischemia secondary to excessive erythropoiesis, New diagnosis of hypertension or worsening of existing hypertension, Cancer related mortality and tumor progression and recurrence, Esophageal and gastric erosions. Number of participants with any AESIs have been presented.

All AEs leading to study intervention discontinuation were collected. Number of participants with any AEs leading to study intervention discontinuation have been presented

Blood samples were collected to analyze the hematology parameter: hematocrit. Baseline value was defined as the last non-missing value prior to the start date and time of the study medication (Day 1). Change from Baseline was calculated as the value at indicated time point minus the value at Baseline.

Blood samples were collected to analyze the hematology parameter: Reticulocytes/Erythrocytes. Baseline value was defined as the last non-missing value prior to the start date and time of the study medication (Day 1). Change from Baseline was calculated as the value at indicated time point minus the value at Baseline.

Blood samples were collected to analyze the hematology parameter: Erythrocytes. Baseline value was defined as the last non-missing value prior to the start date and time of the study medication (Day 1). Change from Baseline was calculated as the value at indicated time point minus the value at Baseline.

Blood samples were collected to analyze the hematology parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Leukocytes and Platelet count. Baseline value was defined as the last non-missing value prior to the start date and time of the study medication (Day 1). Change from Baseline was calculated as the value at indicated time point minus the value at Baseline.

Blood samples were collected to analyze the hematology parameter: Erythrocytes Mean Corpuscular Volume. Baseline value was defined as the last non-missing value prior to the start date and time of the study medication (Day 1). Change from Baseline was calculated as the value at indicated time point minus the value at Baseline.

Blood samples were collected to analyze the hematology parameter: Erythrocytes Mean Corpuscular Hemoglobin. Baseline value was defined as the last non-missing value prior to the start date and time of the study medication (Day 1). Change from Baseline was calculated as the value at indicated time point minus the value at Baseline.

Blood samples were collected to analyze the clinical chemistry parameters: Calcium, Potassium, Sodium and BUN. Baseline value was defined as the last non-missing value prior to the start date and time of the study medication (Day 1). Change from Baseline was calculated as the value at indicated time point minus the value at Baseline.

Blood samples were collected to analyze the clinical chemistry parameter: Creatinine. Baseline value was defined as the last non-missing value prior to the start date and time of the study medication (Day 1). Change from Baseline was calculated as the value at indicated time point minus the value at Baseline.

Blood samples were collected to analyze the clinical chemistry parameters: ALT, ALP and AST. Baseline value was defined as the last non-missing value prior to the start date and time of the study medication (Day 1). Change from Baseline was calculated as the value at indicated time point minus the value at Baseline.

Blood samples were collected to analyze the clinical chemistry parameters: Bilirubin and Direct Bilirubin. Baseline value was defined as the last non-missing value prior to the start date and time of the study medication (Day 1). Change from Baseline was calculated as the value at indicated time point minus the value at Baseline.

Blood samples were collected to analyze the clinical chemistry parameter: Protein. Baseline value was defined as the last non-missing value prior to the start date and time of the study medication (Day 1). Change from Baseline was calculated as the value at indicated time point minus the value at Baseline.

Blood samples were collected to analyze the clinical chemistry parameter: Ferritin. Baseline value was defined as the last non-missing value prior to the start date and time of the study medication (Day 1). Change from Baseline was calculated as the value at indicated time point minus the value at Baseline.

Blood samples were collected to analyze the clinical chemistry parameter: Transferrin saturation. Transferrin saturation is measured as a percentage, it is the ratio of serum iron and total iron-binding capacity, multiplied by 100. Baseline value was defined as the last non-missing value prior to the start date and time of the study medication (Day 1). Change from Baseline was calculated as the value at indicated time point minus the value at Baseline.

Blood samples were collected to analyze the clinical chemistry parameter: Estimated Glomerular Filtration Rate. Baseline value was defined as the last non-missing value prior to the start date and time of the study medication (Day 1). Change from Baseline was calculated as the value at indicated time point minus the value at Baseline.

Blood samples were collected to analyze the hematology parameter: Prothrombin International Normalized Ratio. It is used to assess the clotting ability of blood. Baseline value was defined as the last non-missing value prior to the start date and time of the study medication (Day 1). Change from Baseline was calculated as the value at indicated time point minus the value at Baseline.

Systolic and diastolic blood pressure (BP) were assessed using an appropriate size cuff preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions (e.g., television, cell phones). Baseline value was defined as the last non-missing value prior to the start date and time of the study medication (Day 1). Change from Baseline was calculated as the value at indicated time point minus the value at Baseline.

Heart rate (HR) were assessed using an appropriate size cuff preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions (e.g., television, cell phones). Baseline value was defined as the last non-missing value prior to the start date and time of the study medication (Day 1). Change from Baseline was calculated as the value at indicated time point minus the value at Baseline.

Weight readings in kilogram (kg) were collected. Baseline value was defined as the last non-missing value prior to the start date and time of the study medication (Day 1). Change from Baseline was calculated as the value at indicated time point minus the value at Baseline.

Height readings in centimeters (cm) were collected. Baseline value was defined as the last non-missing value prior to the start date and time of the study medication (Day 1). Change from Baseline was calculated as the value at indicated time point minus the value at Baseline.

Blood samples were collected from all participants for measurement of Hgb values in grams per deciliter (g/dL). Baseline value was defined as the last non-missing value prior to the start date and time of the study medication (Day 1). Hgb results of participants with intercurrent events were excluded from the summary.

Blood samples were collected from all participants for measurement of Hgb values in g/dL. Baseline value was defined as the last non-missing value prior to the start date and time of the study medication (Day 1). Change from Baseline was calculated as the value at indicated time point minus the value at Baseline. Hgb results of participants with intercurrent events were excluded from the summary.

Number of participants with Hgb values above, below, and within the target range (10 to 12 g/dL) were assessed. Baseline assessment was defined as the last non-missing value prior to the start date and time of the study drug (Day 1). Hgb results of participants with intercurrent events were excluded from the summary.

Daprodustat dose was adjusted, if required, one step at a time in the range of 1 to 24 mg, to maintain the target range for Hgb between 10 to 12 g/dL. Dose change values of daprodustat from starting dose at each study time point were calculated as dose level at indicated time point minus starting dose at Day 1 (Baseline).

Number of participants who required daprodustat dose adjustments form the starting dose were assessed. Data were categorized for number of participants who required no dose change (0 times) to 10 times and >10 times dose adjustments during the study.

Mean and standard deviation of daprodustat dose received by participants at each study time point has been presented.

Blood samples were collected for the plasma concentrations of daprodustat from which pharmacokinetic (PK) parameters were determined. Mean and standard deviation of daprodustat Cmax at steady state obtained via modeling in each sub-trial (requiring Dialysis and not yet requiring Dialysis).

Blood samples were collected for the plasma concentrations of daprodustat from which PK parameters were determined. Mean and standard deviation of daprodustat AUC at steady state obtained via modeling in each sub-trial (requiring Dialysis and not yet requiring Dialysis).

Blood samples were collected for the plasma concentrations of daprodustat and metabolites from which PK parameters were determined. Mean and standard deviation of raw daprodustat and metabolites (GSK2391220, GSK2487818, GSK2506102, GSK2506104, GSK2531398 and GSK2531401) at steady state at pre-dose obtained via modeling in each sub-trial (requiring Dialysis and not yet requiring Dialysis).