Anemia Study in Chronic Kidney Disease (CKD): Erythropoiesis Via a Novel Prolyl Hydroxylase Inhibitor (PHI) Daprodustat-Blood Pressure (ASCEND-BP)

A Randomized, Open-label Study to Evaluate the Effect of Daprodustat on Blood Pressure in Subjects With Anemia Associated With Chronic Kidney Disease on Hemodialysis Switched From a Stable Dose of an Erythropoiesis-stimulating Agent

This will be an open-label, randomized, parallel-group study in hemodialysis-dependent (HD) participants with anemia associated with chronic kidney disease (CKD), designed to compare the effects of daprodustat to epoetin alfa on blood pressure (BP). Participants will be screened for eligibility within 7 and 30 days prior to erythropoesis-stimulating agent (ESA) washout. Following a 2-week ESA washout period, on Day 1 participants will be randomized 1:1 and stratified by prior ESA dose before they undergo Acute Challenge 1, a single dose challenge to compare the acute effects on BP of the highest planned once-daily maintenance dose of daprodustat (24 milligrams [mg]) to the highest starting dose of epoetin alfa (100 units/kilogram [U/kg]). This will be followed by an 8-week hemoglobin (Hgb)-maintenance period, where doses of either daprodustat or epoetin alfa will be administered and adjusted. At the end of Hgb maintenance period, on Day 57 an Acute Challenge 2 will be repeated utilizing the same treatment dose administered in Acute Challenge 1; there will be a follow-up visit within 14+/-3 days after completing treatment.

Study Overview

• Status: Completed
• Conditions: Anaemia
• Intervention / Treatment: Drug: Epoetin alfa; Drug: Daprodustat

• Study Type: Interventional
• Enrollment (Actual): 105
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • La Mesa, California, United States, 91942
      • GSK Investigational Site
  • Colorado
    • Lakewood, Colorado, United States, 80228
      • GSK Investigational Site
  • Florida
    • Coral Gables, Florida, United States, 33134
      • GSK Investigational Site
    • DeLand, Florida, United States, 32720
      • GSK Investigational Site
    • Hollywood, Florida, United States, 33024
      • GSK Investigational Site
    • Miami, Florida, United States, 33133
      • GSK Investigational Site
    • Orlando, Florida, United States, 32809
      • GSK Investigational Site
  • Illinois
    • Chicago, Illinois, United States, 60643
      • GSK Investigational Site
  • Minnesota
    • Minneapolis, Minnesota, United States, 55404
      • GSK Investigational Site
  • South Carolina
    • Spartanburg, South Carolina, United States, 29301
      • GSK Investigational Site
  • Texas
    • San Antonio, Texas, United States, 78215
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria

• More than or equal to 40 years of age, at the time of signing the informed consent
• Stable Hgb 8.5 to 11.5 grams per deciliter (g/dL) inclusive.
• Dialysis frequency: On hemodialysis (HD, hemofiltration or hemodiafiltration) three-to five-times weekly for at least 4 weeks prior to screening.
• A single pool Kt/Vurea >=1.2 based on a historical value obtained within 3 months prior to screening in order to ensure the adequacy of dialysis. If Kt/Vurea is not available, then an average of the last 2 values of urea reduction ratio should be at least 65 percent (%).
• Treated with an ESA (epoetins or their biosimilars, darbepoetin, or methoxy polyethylene glycol [PEG]-epoetin beta) for at least 4 weeks prior to screening.
• Participants may be on stable (<=50% change in overall dose and compliance of 80% of prescribed doses in the 4 weeks prior to and including the screening period) maintenance oral or intravenous (IV; <=100 mg/week) iron supplementation. If participants are on oral or IV iron, then doses must be stable for the 4 weeks prior to Washout.
• Weight: Mid-week weight change between dialysis treatments <5% as assessed post-dialysis at the Screening and Washout visits.
• On at least 1 antihypertensive medication (excluding diuretics) and on that same medication and the same dose for at least 1 week prior to Washout.
• Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the consent form and the protocol.
• Willing and able to wear ABPM device for at least 25 hours on two separate sessions.

Exclusion Criteria

• Planned change from HD to peritoneal dialysis within the study time period, or on home dialysis.
• Planned for kidney transplant within the 16 weeks following the Screening visit.
• An epoetin alfa dose of >=360 U/kg/week IV or >=250 U/kg/week subcutaneous (SC), or darbepoetin dose of >=1.8 micrograms (μg)/kg/week IV or SC, or methoxy PEG-epoetin beta dose of >=2.2 μg/kg/week within the 8 weeks prior to screening through Week -4.
• Planned or recorded administration of Mircera (methoxy PEG-epoetin beta) within the 4 weeks prior to the Washout.
• Occurrence of myocardial infarction or acute coronary syndrome within 3 months prior to Washout.
• Stroke or transient ischemic attack within 3 months prior to Washout.
• Chronic Class 4 heart failure, as defined by the New York Heart Association functional classification system diagnosed prior to Washout.
• QT interval corrected for heart rate using Bazett's formula (QTcB) >500 milliseconds (msec), or QTcB >530 msec in participants with Bundle Branch Block. There is no QTc exclusion for participants with a predominantly paced rhythm.
• Resting post dialysis SBP >160 millimeters of mercury (mmHg); or DBP >100 mmHg at screening or uncontrolled hypertension as determined by the investigator.
• Presence of atrial fibrillation.
• Active chronic inflammatory disease that could impact erythropoiesis (e.g., scleroderma, systemic lupus erythematosus, rheumatoid arthritis, celiac disease) diagnosed prior to Washout.
• History of bone marrow aplasia or pure red cell aplasia.
• Other causes of anemia including Pernicious anemia, thalassemia major, sickle cell disease or myelodysplastic syndrome.
• Alanine transaminase (ALT) >2 times upper limit of normal (ULN) (screening only) or Bilirubin >1.5 times ULN (screening only) or Current unstable liver or biliary disease per investigator assessment, generally defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice, or cirrhosis.
• Major surgery (excluding vascular access surgery) within the 3 months prior to Washout or planned during the study.
• Blood transfusion within the 8 weeks prior to Washout or an anticipated need for blood transfusion during the study.
• Evidence of actively bleeding gastric, duodenal, or esophageal ulcer disease or clinically significant gastrointestinal bleeding within the 8 weeks prior to Washout.
• Clinical evidence of acute infection or history of infection requiring IV antibiotic therapy within the 8 weeks prior to Washout.
• History of malignancy within the two years prior to screening through Day 1 or currently receiving treatment for cancer, or has a known complex kidney cyst (e.g., Bosniak Category IIF, III or IV) >=3 centimeters.
• Participants with an upper arm diameter which cannot be measured by oscillometer/ sphygmomanometer cuff or for whom BP cannot be measured in the opposite arm of current vascular access.
• History of severe allergic or anaphylactic reactions or hypersensitivity to excipients in the investigational product.
• Use of any prescription or non-prescription drugs or dietary supplements that are prohibited from screening until Washout.
• The participant has participated in a clinical trial and has received an experimental investigational product within the 30 days prior to Day 1 or within 5 half lives of the investigational product prior to screening, whichever is longer.
• Any other condition, clinical or laboratory abnormality, or examination finding that the investigator considers would put the participant at unacceptable risk, which may affect study compliance or prevent understanding of the aims or investigational procedures or possible consequences of the study.
• A female participant is pregnant (as confirmed by a positive serum human chorionic gonadotrophin test for females of reproductive potential only), participant is breastfeeding, or participant is of reproductive potential and does not agree to follow one of the pre-specified contraceptive options
• Vitamin B12 at or below the lower limit of the reference range (may rescreen in a minimum of 8 weeks, following treatment).
• Folate at <2.0 nanograms/milliliter (ng/mL) (4.5 Nanomoles per Liter) (may rescreen in a minimum of 4 weeks, following treatment).
• Ferritin at <100 ng/mL
• Transferrin saturation at <20%.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Participants receiving Epoetin alfa; On Day 1, participants will undergo 24-hour Acute Challenge 1, in which participants will receive a single dose of 100 U/kg epoetin alfa IV. After completing Acute Challenge 1, participants will enter in an 8-week Hgb maintenance period. At the end of Hgb maintenance period, on Day 57, Acute Challenge 2 will be performed utilizing the same treatment dose administered in Acute Challenge 1.	Drug: Epoetin alfa; Epoetin alfa will be administered according to local labelling and clinical practice guidelines to keep Hgb in the target range (10.0-11.0 g/dL)
EXPERIMENTAL: Participants receiving Daprodustat; On Day 1, participants will undergo 24-hour Acute Challenge 1, in which participants will receive 24 mg daprodustat. After completing Acute Challenge 1, participants will enter an 8-week Hgb maintenance period. At the end of Hgb maintenance period, on Day 57, Acute Challenge 2 will be performed utilizing the same treatment dose administered in Acute Challenge 1.	Drug: Daprodustat; Daprodustat will be available as oral tablets at unit dose strength of 1, 2, 4, 6, 8 and 10 mg.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Average of Systolic Blood Pressure (SBP) Measured by Ambulatory Blood Pressure Monitoring (ABPM) Over 6-hour Post Dosing on Day 57	The effect of daprodustat and epoetin alfa on blood pressure was compared using ABPM after 8 weeks of Hgb maintenace therapy on Day 57. Analysis was based on "analysis of covariance (ANCOVA) with terms for treatment, prior erythropoiesis-stimulating agent (ESA) dose (low/high), post-Hemodialysis dependent (HD)/pre-AC 1 SBP, difference between post-HD/pre-AC 2 SBP and post-HD/pre-AC 1 SBP and treatment by difference in post-HD SBP between AC 1 and 2 interaction." Least square (LS) mean of 6 hour average SBP post AC2 on Day 57 and its corresponding standard error has been presented.	Up to 6 hours post dose on Day 57

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Average of SBP, Diastolic Blood Pressure (DBP) and Mean Arterial Blood Pressure (MAP) Measured by ABPM Over 6-hour Post Dosing on Day 1	The initial effect of daprodustat and epoetin alfa on blood pressure was compared using ABPM over 6 hour post-dosing on Day 1. Analysis was based on ANCOVA with terms for treatment, prior ESA dose (low/high), post-HD/pre-AC1 SBP, DBP and MAP. LS mean of 6 hour average SBP, DBP and MAP post AC1 on Day 1 and its corresponding standard error has been presented.	Up to 6 hours post dose on Day 1
Average of Heart Rate (HR) Measured by ABPM Over 6 Hour Post Dosing on Day 1	The initial effect of daprodustat and epoetin alfa on HR was compared using ABPM over 6 hour post-dosing on Day 1. Analysis was based on ANCOVA with terms for treatment, prior ESA dose (low/high), post-HD/pre-AC1 HR. LS mean of 6 hour average HR post AC1 on Day 1 and its corresponding standard error has been presented.	Up to 6 hours post dose on Day 1
Area Under the Effect Curve (AUEC) of SBP, DBP and MAP Measured by ABPM Over 24-hour Post Dosing on Day 1	The initial effect of daprodustat and epoetin alfa on blood pressure was compared using AUEC of SBP, DBP and MAP measured by ABPM over 24-hour post dosing on Day 1. Analysis was based on ANCOVA with terms for treatment and prior ESA dose (low/high). LS mean of AUEC up to 24 hours post dose on Day 1 and its corresponding standard error has been presented.	Up to 24 hours post dose on Day 1
AUEC of HR Measured by ABPM Over 24-hour Post Dosing on Day 1	The initial effect of daprodustat and epoetin alfa on HR was compared using AUEC of HR measured by ABPM over 24-hour post dosing. Analysis was based on ANCOVA with terms for treatment and prior ESA dose (low/high). LS mean of AUEC up to 24 hours post dose on Day 1 and its corresponding standard error has been presented.	Up to 24 hours post dose on Day 1
Average of DBP and MAP Measured by ABPM Over 6-hour Post Dosing on Day 57	The effect of daprodustat and epoetin alfa on blood pressure was compared using ABPM over 6 hour post-dosing after AC2 on Day 57. Analysis was based on ANCOVA with terms for treatment, prior ESA dose (low/high), post-HD/pre-AC1 DBP and MAP, difference between post-HD/pre-AC2 DBP and MAP and post-HD/pre-AC1 DBP and MAP and treatment by difference in post-HD DBP and MAP between AC1 and 2 interaction. LS mean of 6 hour average DBP and MAP post AC2 on Day 57 and its corresponding standard error has been presented.	Up to 6 hours post dose on Day 57
Average of HR Measured by ABPM Over 6 Hour Post Dosing on Day 57	The effect of daprodustat and epoetin alfa on HR was compared using ABPM over 6 hour post-dosing. Analysis was based on ANCOVA with terms for treatment, prior ESA dose (low/high), post-HD/pre-AC1 HR, difference between post-HD/pre-AC2 HR and post-HD/pre-AC1 HR and treatment by difference in post-HD HR between AC1 and 2 interaction. LS mean of 6 hour average HR post AC2 on Day 57 and its corresponding standard error has been presented.	Up to 6 hours post dose on Day 57
AUEC of SBP, DBP and MAP Measured by ABPM Over 24-hour Post Dosing on Day 57	The effect of daprodustat and epoetin alfa on blood pressure was compared using AUEC of SBP, DBP and MAP measured by ABPM over 24-hour post dosing on Day 57. Analysis was based on ANCOVA with terms for treatment and prior ESA dose (low/high). LS mean of AUEC up to 24 hour post dose on Day 57 and its corresponding standard error has been presented.	Up to 24 hours post dose on Day 57
AUEC of HR Measured by ABPM Over 24-hour Post Dosing on Day 57	The effect of daprodustat and epoetin alfa on HR was compared using AUEC of HR measured by ABPM over 24-hour post dosing on Day 57. Analysis was based on ANCOVA with terms for treatment and prior ESA dose (low/high). LS mean of AUEC up to 24 hour post dose on Day 57 and its corresponding standard error has been presented.	Up to 24 hours post dose on Day 57
Change From Pre-dose in SBP, DBP and MAP at Day 1	The change from pre-dose in SBP, DBP and MAP was measured using ABPM to compare the initial effect of daprodustat to epoetin alfa after AC1 on Day 1. Change from pre-dose at each timepoint is calculated as measurement at post-dose minus pre-acute challenge 1 measurement.	Day 1: Pre-dose and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23 and 24 hours post-dose
Change From Pre-dose in HR at Day 1	The change from pre-dose in HR was measured using ABPM to compare the initial effect of daprodustat to epoetin alfa after AC1 on Day 1. Change from pre-dose at each timepoint is calculated as measurement at post-dose minus pre-acute challenge 1 measurement.	Day 1: Pre-dose and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23 and 24 hours post-dose
Plasma Concentrations of Daprodustat	Blood samples were collected at indicated time points for the concentrations of daprodustat.	Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours on Days 1 and 57
Plasma Concentrations of Metabolite GSK2391220	Blood samples were collected at indicated time points for the concentrations of metabolite GSK2391220.	Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours on Days 1 and 57
Plasma Concentrations of Metabolite GSK2506104	Blood samples were collected at indicated time points for the concentrations of metabolite GSK2506104.	Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours on Days 1 and 57
Plasma Concentrations of Metabolite GSK2487818	Blood samples were collected at indicated time points for the concentrations of metabolite GSK2487818.	Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours on Days 1 and 57
Plasma Concentrations of Metabolite GSK2506102	Blood samples were collected at indicated time points for the concentrations of metabolite GSK25206102.	Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours on Days 1 and 57
Plasma Concentrations of Metabolite GSK2531398	Blood samples were collected at indicated time points for the concentrations of metabolite GSK2531398.	Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours on Days 1 and 57
Plasma Concentrations of Metabolite GSK2531401	Blood samples were collected at indicated time points for the concentrations of metabolite GSK2531401.	Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours on Days 1 and 57
Maximum Plasma Concentration (Cmax) of Daprodustat, GSK2391220, GSK2487818, GSK2506102, GSK2506104, GSK2531398 and GSK2531401	Blood samples were collected at indicated time points for pharmacokinetic analysis of daprodustat and its metabolites GSK2391220, GSK2487818, GSK2506102, GSK2506104, GSK2531398 and GSK2531401. PK parameters were analyzed using standard non-compartmental analysis.	Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours on Days 1 and 57
Time of Occurrence of Cmax (Tmax) of Daprodustat, GSK2391220, GSK2487818, GSK2506102, GSK2506104, GSK2531398 and GSK2531401	Blood samples were collected at indicated time points for pharmacokinetic analysis of daprodustat and its metabolites GSK2391220, GSK2487818, GSK2506102, GSK2506104, GSK2531398 and GSK2531401. PK parameters were analyzed using standard non-compartmental analysis.	Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours on Days 1 and 57
Terminal Phase Half-life (t1/2) of Daprodustat, GSK2391220, GSK2487818, GSK2506102, GSK2506104, GSK2531398 and GSK2531401	Blood samples were collected at indicated time points for pharmacokinetic analysis of daprodustat and its metabolites GSK2391220, GSK2487818, GSK2506102, GSK2506104, GSK2531398 and GSK2531401. PK parameters were analyzed using standard non-compartmental analysis.	Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours on Days 1 and 57
Area Under Concentration-time Curve From Time Zero to 24 Hours (AUC[0-24]) of Daprodustat, GSK2391220, GSK2487818, GSK2506102, GSK2506104, GSK2531398 and GSK2531401	Blood samples were collected at indicated time points for pharmacokinetic analysis of daprodustat and its metabolites GSK2391220, GSK2487818, GSK2506102, GSK2506104, GSK2531398 and GSK2531401. PK parameters were analyzed using standard non-compartmental analysis.	Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours on Days 1 and 57

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Any Serious Adverse Events (SAEs)	Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly or birth defect or any other situation according to medical or scientific judgment was categorized as SAE.	Up to Week 10
Number of Participants With Treatment Emergent Common (>=2%) Non-serious Adverse Events (Non-SAEs)	An AE is any untoward medical occurrence that occurs in a participant or clinical investigation participant administered a pharmaceutical product, and which does not necessarily have to have a causal relationship with study treatment. Number of participants with treatment emergent common (>=2% non-SAEs in each arm) non-SAEs has been presented.	Up to Week 8
Number of Participants Who Discontinued the Study Treatment	Number of participants who discontinued the study treatment due to any reason are presented. The reasons for discontinuation included adverse events, protocol specified withdrawal criteria met, physician decision and withdrawal by participant.	Up to Week 10
Absolute Values for Clinical Chemistry Parameters: Albumin and Protein	Blood samples were collected for the analysis of clinical chemistry parameters including albumin and protein. Baseline value (Day1) is the latest non-missing pre-dose assessment.	Baseline (Day 1) and at Days 29, 57 and Week 10
Absolute Values for Clinical Chemistry Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST)	Blood samples were collected for the analysis of clinical chemistry parameters including ALP, ALT and AST. Baseline value (Day1) is the latest non-missing pre-dose assessment.	Baseline (Day 1) and at Days 29, 57 and Week 10
Absolute Values for Clinical Chemistry Parameters: Direct Bilirubin, Total Bilirubin and Indirect (Indrt) Bilirubin	Blood samples were collected for the analysis of clinical chemistry parameters including direct bilirubin, total bilirubin and Indrt bilirubin. Baseline value (Day1) is the latest non-missing pre-dose assessment.	Baseline (Day 1) and at Days 29, 57 and Week 10
Absolute Values for Clinical Chemistry Parameters: Calcium Corrected for Albumin (CCA), Glucose, Potassium, Phosphate and Sodium	Blood samples were collected for the analysis of clinical chemistry parameters including CCA, glucose, potassium, phosphate and sodium. Baseline value (Day1) is the latest non-missing pre-dose assessment.	Baseline (Day 1) and at Days 29, 57 and Week 10
Change From Baseline Values for Clinical Chemistry Parameters: Albumin and Protein	Blood samples were collected for the analysis of clinical chemistry parameters including albumin and protein. Baseline value (Day1) is the latest non-missing pre-dose assessment. Change from Baseline is defined as Post-dose visit value minus Baseline value.	Baseline (Day 1) and at Days 29, 57 and Week 10
Change From Baseline Values for Clinical Chemistry Parameters: ALP, ALT and AST	Blood samples were collected for the analysis of clinical chemistry parameters including ALP, ALT and AST. Baseline value (Day1) is the latest non-missing pre-dose assessment. Change from Baseline is defined as Post-dose visit value minus Baseline value.	Baseline (Day 1) and at Days 29, 57 and Week 10
Change From Baseline Values for Clinical Chemistry Parameters: Direct Bilirubin, Total Bilirubin and Indrt. Bilirubin	Blood samples were collected for the analysis of clinical chemistry parameters including direct bilirubin, total bilirubin and indrt. bilirubin. Baseline value (Day1) is the latest non-missing pre-dose assessment. Change from Baseline is defined as Post-dose visit value minus Baseline value.	Baseline (Day 1) and at Days 29, 57 and Week 10
Change From Baseline Values for Clinical Chemistry Parameters: CCA, Glucose, Potassium, Phosphate and Sodium	Blood samples were collected for the analysis of clinical chemistry parameters including CCA, glucose, potassium, phosphate and sodium. Baseline value (Day1) is the latest non-missing pre-dose assessment. Change from Baseline is defined as Post-dose visit value minus Baseline value.	Baseline (Day 1) and at Days 29, 57 and Week 10
Absolute Values for Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets and Leukocytes	Blood samples were collected for the analysis of hematology parameters including basophils, eosinophils, lymphocytes, monocytes, neutrophils, platelets and leukocytes. Baseline value (Day1) is the latest non-missing pre-dose assessment.	Baseline (Day 1) and at Days 29, 57 and Week 10
Absolute Values for Hematology Parameter: Hematocrit	Blood samples were collected for the analysis of hematology parameter: hematocrit. Baseline value (Day1) is the latest non-missing pre-dose assessment.	Baseline (Day 1) and at Days 29, 57 and Week 10
Absolute Values for Hematology Parameters: Erythrocytes and Reticulocytes	Blood samples were collected for the analysis of hematology parameters: erythrocytes and reticulocytes. Baseline value (Day1) is the latest non-missing pre-dose assessment.	Baseline (Day 1) and at Days 29, 57 and Week 10
Absolute Values for Hematology Parameters: Hemoglobin and Erythrocyte Mean Corpusclar Hemoglobin Concentration ( Ery. MCHC)	Blood samples were collected for the analysis of hematology parameters: hemoglobin and ery.MCHC. Baseline value (Day1) is the latest non-missing pre-dose assessment.	Baseline (Day 1) and at Days 29, 57 and Week 10
Absolute Values for Hematology Parameter: Ery. Mean Corpuscular Hemoglobin (MCH) and Reticulocyte Corpuscular Hemoglobin Content (CHr)	Blood samples were collected for the analysis of hematology parameter: ery.MCH and CHr. Baseline value (Day1) is the latest non-missing pre-dose assessment.	Baseline (Day 1) and at Days 29, 57 and Week 10
Absolute Values for Hematology Parameter: Ery. Mean Corpuscular Volume (MCV)	Blood samples were collected for the analysis of hematology parameter: ery.MCV. Baseline value (Day1) is the latest non-missing pre-dose assessment.	Baseline (Day 1) and at Days 29, 57 and Week 10
Absolute Values for Hematology Parameter: Erythrocyte Distribution Width	Blood samples were collected for the analysis of hematology parameter: erythrocyte distribution width. Baseline value (Day1) is the latest non-missing pre-dose assessment.	Baseline (Day 1) and at Days 29, 57 and Week 10
Change From Baseline Values for Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets and Leukocytes	Blood samples were collected for the analysis of hematology parameters including basophils, eosinophils, lymphocytes, monocytes, neutrophils, platelets and leukocytes. Baseline value (Day1) is the latest non-missing pre-dose assessment. Change from Baseline is defined as Post-dose visit value minus Baseline value.	Baseline (Day 1) and at Days 29, 57 and Week 10
Change From Baseline Values for Hematology Parameter: Hematocrit	Blood samples were collected for the analysis of hematology parameter: hematocrit. Baseline value (Day1) is the latest non-missing pre-dose assessment. Change from Baseline is defined as Post-dose visit value minus Baseline value.	Baseline (Day 1) and at Days 29, 57 and Week 10
Change From Baseline Values for Hematology Parameters: Erythrocytes and Reticulocytes	Blood samples were collected for the analysis of hematology parameters: erythrocytes and reticulocytes. Baseline value (Day1) is the latest non-missing pre-dose assessment. Change from Baseline is defined as Post-dose visit value minus Baseline value.	Baseline (Day 1) and at Days 29, 57 and Week 10
Change From Baseline Values for Hematology Parameters: Hemoglobin and Ery. MCHC	Blood samples were collected for the analysis of hematology parameters: hemoglobin and ery.MCHC. Baseline value (Day1) is the latest non-missing pre-dose assessment. Change from Baseline is defined as Post-dose visit value minus Baseline value.	Baseline (Day 1) and at Days 29, 57 and Week 10
Change From Baseline Values for Hematology Parameters: Ery. MCH and CHr	Blood samples were collected for the analysis of hematology parameter: ery.MCH and CHr. Baseline value (Day1) is the latest non-missing pre-dose assessment. Change from Baseline is defined as Post-dose visit value minus Baseline value.	Baseline (Day 1) and at Days 29, 57 and Week 10
Change From Baseline Values for Hematology Parameter: Ery. MCV	Blood samples were collected for the analysis of hematology parameter: ery.MCV. Baseline value (Day1) is the latest non-missing pre-dose assessment. Change from Baseline is defined as Post-dose visit value minus Baseline value.	Baseline (Day 1) and at Days 29, 57 and Week 10
Change From Baseline Values for Hematology Parameter: Erythrocyte Distribution Width	Blood samples were collected for the analysis of hematology parameter: erythrocyte distribution width. Baseline value (Day1) is the latest non-missing pre-dose assessment. Change from Baseline is defined as Post-dose visit value minus Baseline value.	Baseline (Day 1) and at Days 29, 57 and Week 10
Absolute Values for Electrocardiogram (ECG) Mean Heart Rate	Full 12-lead ECGs were obtained in supine position using an ECG machine to measure mean heart rate. Baseline (Day 1-predose) is the latest non-missing pre-dose assessment.	Baseline (Day 1-predose) and at Day 1: 24 hours; Day 57: pre-dose; Day 57: 24 hours and Week 10
Absolute Values for ECG Parameters: PR Interval, QRS Duration, QT Interval Corrected for Heart Rate (QTc) and QT Interval Corrected for Heart Rate Using Bazett's Formula (QTcB)	Full 12-lead ECGs were obtained in supine position using an ECG machine to measure ECG parameters: PR interval, QRS duration, QTc interval and QTcB. Baseline (Day 1-predose) is the latest non-missing pre-dose assessment.	Baseline (Day 1-predose) and at Day 1: 24 hours; Day 57: pre-dose; Day 57: 24 hours and Week 10
Change From Baseline Values for ECG Mean Heart Rate	Full 12-lead ECGs were obtained in supine position using an ECG machine to measure mean heart rate. Baseline (Day 1-predose) is the latest non-missing pre-dose assessment. Change from Baseline is defined as Post-dose visit value minus Baseline value.	Baseline (Day 1-predose) and at Day 1: 24 hours; Day 57: pre-dose; Day 57: 24 hours and Week 10
Change From Baseline Values for ECG Parameters: PR Interval, QRS Duration, QTc and QTcB	Full 12-lead ECGs were obtained in supine position using an ECG machine to measure ECG parameters: PR interval, QRS duration, QTc interval and QTcB. Baseline (Day 1-predose) is the latest non-missing pre-dose assessment. Change from Baseline is defined as Post-dose visit value minus Baseline value.	Baseline (Day 1-predose) and at Day 1: 24 hours; Day 57: pre-dose; Day 57: 24 hours and Week 10
Absolute Values for Vital Signs: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)	Vital signs including SBP and DBP were measured in participants in a semi-supine position after 5 minutes rest. Baseline (Day 1-predose) is the latest non-missing pre-dose assessment.	Baseline (Day 1, predose) and at Day 1: 3, 12, 24 hours; Day 29: pre- and post-dialysis; Day 57: pre- and post-dialysis, 3, 12, 24 hours and Week 10: pre- and post-dialysis
Absolute Values for Temperature	Temperature was measured in participants in a semi-supine position after 5 minutes rest. Baseline (Day 1-predose) is the latest non-missing pre-dose assessment.	Baseline (Day 1, predose) and at Day 1: 3, 12, 24 hours; Day 29: pre- and post-dialysis; Day 57: pre- and post-dialysis, 3, 12, 24 hours and Week 10: pre- and post-dialysis
Absolute Values for Pulse Rate	Pulse rate was measured in participants in a semi-supine position after 5 minutes rest. Baseline (Day 1-predose) is the latest non-missing pre-dose assessment.	Baseline (Day 1, predose) and at Day 1:3, 12, 24 hours; Day 29: pre- and post-dialysis; Day 57: pre- and post-dialysis, 3, 12, 24 hours and Week 10: pre- and post-dialysis
Change From Baseline Values for Vital Signs: SBP and DBP	Vital signs including SBP and DBP were measured in participants in a semi-supine position after 5 minutes rest. Baseline (Day 1-predose) is the latest non-missing pre-dose assessment. Change from Baseline is defined as Post-dose visit value minus Baseline value.	Baseline (Day 1, predose) and at Day 1: 3, 12, 24 hours; Day 29: pre- and post-dialysis; Day 57: pre- and post-dialysis, 3, 12, 24 hours and Week 10: pre- and post-dialysis
Change From Baseline Values for Temperature	Temperature was measured in participants in a semi-supine position after 5 minutes rest. Baseline (Day 1-predose) is the latest non-missing pre-dose assessment. Change from Baseline is defined as Post-dose visit value minus Baseline value.	Baseline (Day 1, predose) and at Day 1: 3, 12, 24 hours; Day 29: pre- and post-dialysis; Day 57: pre- and post-dialysis, 3, 12, 24 hours and Week 10: pre- and post-dialysis
Change From Baseline Values for Pulse Rate	Pulse rate was measured in participants in a semi-supine position after 5 minutes rest. Baseline (Day 1-predose) is the latest non-missing pre-dose assessment. Change from Baseline is defined as Post-dose visit value minus Baseline value.	Baseline (Day 1, predose) and at Day 1: 3, 12, 24 hours; Day 29: pre- and post-dialysis; Day 57: pre- and post-dialysis, 3, 12, 24 hours and Week 10: pre- and post-dialysis

Collaborators and Investigators

• Sponsor: GlaxoSmithKline
• Collaborators: Quintiles, Inc.; ERT: Clinical Trial Technology Solutions; Q2 Solutions; HemoCue

Publications and helpful links

General Publications

• Natale P, Palmer SC, Jaure A, Hodson EM, Ruospo M, Cooper TE, Hahn D, Saglimbene VM, Craig JC, Strippoli GF. Hypoxia-inducible factor stabilisers for the anaemia of chronic kidney disease. Cochrane Database Syst Rev. 2022 Aug 25;8(8):CD013751. doi: 10.1002/14651858.CD013751.pub2.

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 27, 2017
• Primary Completion (ACTUAL): July 9, 2020
• Study Completion (ACTUAL): July 9, 2020

Study Registration Dates

• First Submitted: January 20, 2017
• First Submitted That Met QC Criteria: January 20, 2017
• First Posted (ESTIMATE): January 24, 2017

Study Record Updates

• Last Update Posted (ACTUAL): June 3, 2021
• Last Update Submitted That Met QC Criteria: June 2, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: Anemia; CKD; Blood pressure; ESA; Daprodustat
• Additional Relevant MeSH Terms: Urologic Diseases; Hematologic Diseases; Renal Insufficiency; Kidney Diseases; Renal Insufficiency, Chronic; Anemia; Hematinics; Epoetin Alfa
• Other Study ID Numbers: 205665

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
• IPD Sharing Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints of the study.
• IPD Sharing Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No