Study to Evaluate the Efficacy, Safety and Pharmacokinetics of Three-times Weekly Dosing of GSK1278863 in Hemodialysis-dependent Subjects With Anemia Associated With Chronic Kidney Disease Who Are Switched From a Stable Dose of an Erythropoiesis-stimulating Agent

Sponsor

GlaxoSmithKline (Industry)

Overall Status

Completed

CT.gov ID

NCT02689206

Collaborator

(none)

103

Enrollment

Locations

Arms

11.3

Actual Duration (Months)

2.7

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

GSK1278863 is an orally available, hypoxia-inducible factor - prolyl hydroxylase inhibitor, currently being investigated as a treatment for anemia associated with chronic kidney disease. GSK1278863 has been given as a once daily regimen in clinical studies to date. However, physicians in countries that use a three-times weekly hemodialysis schedule prefer to give the anemia medicine at the same time as the dialysis session. This study will test how well GSK1278863 can maintain hemoglobin levels when given three-times weekly, for 29 days.

This study will describe the relationship between hemoglobin and GSK1278863 given three-times weekly. The data from this study will allow for conversion of once daily doses to three-times weekly doses.

Condition or Disease	Intervention/Treatment	Phase
Anaemia	Drug: GSK1278863 Drug: GSK1278863 matching Placebo	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

103 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

A 29-day, Randomized, Double-blinded, Placebo-controlled, Parallel-group, Multi-center Study to Evaluate the Efficacy, Safety and Pharmacokinetics of Three-times Weekly Dosing of GSK1278863 in Hemodialysis-dependent Subjects With Anemia Associated With Chronic Kidney Disease Who Are Switched From a Stable Dose of an Erythropoiesis-stimulating Agent

Actual Study Start Date :

Feb 17, 2016

Actual Primary Completion Date :

Jan 25, 2017

Actual Study Completion Date :

Jan 25, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: GSK1278863 10 mg Subject will receive 10 mg of GSK1278863 three-times weekly for 4 weeks (up to 29 days).	Drug: GSK1278863 GSK1278863 will be supplied as a round, biconvex, 10 millimeter (mm) white film coated tablet with the unit dose strength of 5 mg and 25 mg.
Experimental: GSK1278863 15 mg Subject will receive 15 mg of GSK1278863 three-times weekly for 4 weeks (up to 29 days).	Drug: GSK1278863 GSK1278863 will be supplied as a round, biconvex, 10 millimeter (mm) white film coated tablet with the unit dose strength of 5 mg and 25 mg.
Experimental: GSK1278863 25 mg Subject will receive 25 mg of GSK1278863 three-times weekly for 4 weeks (up to 29 days).	Drug: GSK1278863 GSK1278863 will be supplied as a round, biconvex, 10 millimeter (mm) white film coated tablet with the unit dose strength of 5 mg and 25 mg.
Experimental: GSK1278863 30 mg Subject will receive 30 mg of GSK1278863 three-times weekly for 4 weeks (up to 29 days).	Drug: GSK1278863 GSK1278863 will be supplied as a round, biconvex, 10 millimeter (mm) white film coated tablet with the unit dose strength of 5 mg and 25 mg.
Placebo Comparator: Placebo Subject will receive GSK1278863 matching placebo three-times weekly for 4 weeks (up to 29 days).	Drug: GSK1278863 matching Placebo GSK1278863 matching placebo will be supplied as a round, biconvex, 10 mm white film coated tablet.

Outcome Measures

Primary Outcome Measures

Change From Baseline in Hgb Levels at Day 29 [Baseline and Day 29]
Blood samples were collected from participants for measurement of Hgb values. Baseline is the average of Hgb measured at Week -2 and Day 1 visits. Change from Baseline at Day 29 was defined as post dose value at Day 29 minus Baseline value. The analysis was performed on intent-to-treat (ITT) Population which comprised of all randomized participants who received at least one dose of study treatment, had a Baseline and at least one corresponding on treatment assessment, including Hgb.

Secondary Outcome Measures

Maximum Observed Change From Baseline in Plasma Erythropoietin (EPO) [Baseline and up to Day 29]
Blood samples were collected at Day 1, Day 15 and Day 29 for pharmacodynamic analysis of effect of dapro three times weekly dose regimens on EPO. Day 1 values were considered as Baseline values. Change from Baseline was calculated by subtracting post-Baseline visit values minus Baseline value. The change from Baseline at each given post-Baseline time point was calculated and the maximum change from Baseline was determined.
Maximum Observed Percent Change From Baseline in Vascular Endothelial Growth Factor (VEGF) [Baseline and up to Day 29]
Blood samples were collected at Day 1, Day 15 and Day 29 for pharmacodynamic analysis of effect of dapro three times weekly dose regimens on VEGF. Day 1 values were considered as Baseline values. The percent change from Baseline at each given post-Baseline time point was calculated (expressed as geometric mean) and the maximum percent change from Baseline was determined.
Percent Change From Baseline in Hepcidin at Day 29 [Baseline and Day 29]
Blood samples were collected at Day 1, Day 15 and Day 29 for pharmacodynamic analysis of effect of dapro three times weekly dose regimens on hepcidin. Day 1 values were considered as Baseline values. The Percent change from Baseline at Day 29 post-Baseline time point was calculated and expressed as geometric mean and the maximum change from Baseline was determined.
Change From Baseline in Hematocrit Levels [Baseline and Day 29]
Blood samples were collected at Day 1, Day 15 and Day 29 for pharmacodynamic analysis of effect Dapro three times weekly dose regimens on hematocrit. Day 1 values were considered as Baseline values. Change from Baseline was calculated by subtracting post-dose visit values minus Baseline value. The change from Baseline at Day 29 post-Baseline time point was calculated.
Change From Baseline in Red Blood Cell (RBC) Count [Baseline and Day 29]
Blood samples were collected at Day 1, Day 15 and Day 29 for pharmacodynamic analysis of effect Dapro three times weekly dose regimens on RBC count. Day 1 values were considered as Baseline values. Change from Baseline was calculated by subtracting post-dose visit values minus Baseline value. The change from Baseline at Day 29 post-Baseline time point was calculated.
Change From Baseline in Reticulocyte Count [Baseline and Day 29]
Blood samples were collected at Day 1, Day 15 and Day 29 for pharmacodynamic analysis of effect Dapro three times weekly dose regimens on reticulocyte count. Day 1 values were considered as Baseline values. Change from Baseline was calculated by subtracting post-Baseline visit values minus Baseline value. The change from Baseline at Day 29 post-Baseline time point was calculated.
Change From Baseline in Reticulocyte Hemoglobin (CHr) [Baseline and Day 29]
Blood samples were collected at Day 1, Day 15 and Day 29 for pharmacodynamic analysis of effect Dapro three times weekly dose regimens on CHr. Day 1 values were considered as Baseline values. Change from Baseline was calculated by subtracting post-Baseline visit values minus Baseline value. The change from Baseline at Day 29 post-Baseline time point was calculated.
Area Under the Curve (AUC) From Time Zero to the Time of the Last Quantifiable Concentration (AUC[0-t]) and AUC From Time Zero to Infinity (AUC[0-inf]) of Dapro [Pre-dose on Day 1; 6-10 hours, 7-11 hours, 8-12 hours, 9-13 hours post dose on Day 15; pre-dose and 1, 2, 3 hours post-dose on Day 29]
Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of dapro. The data from each PK sampling day was combined to generate a single profile, and normalized to a 24-hour period to create a "Day 1" profile for non-compartmental analysis (NCA). Metabolite plasma concentrations were analyzed but PK parameters could not be calculated as the metabolites were partially eliminated through dialysis and the dialysis start and end times were not consistent on both PK days. Therefore, a representative metabolite PK profile could not be generated. The analysis was performed on PK Population, which comprised of all participants from whom a PK sample has been obtained and analyzed. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).
Maximum Observed Concentration of Dapro in Plasma (Cmax) [Pre-dose on Day 1; 6-10 hours, 7-11 hours, 8-12 hours, 9-13 hours post dose on Day 15; pre-dose and 1, 2, 3 hours post-dose on Day 29]
Blood samples were collected at indicated time points for PK analysis of dapro. The data from each PK sampling day was combined to generate a single profile, and normalized to a 24-hour period to create a "Day 1" profile for NCA. Metabolite plasma concentrations were analyzed but PK parameters could not be calculated as the metabolites were partially eliminated through dialysis and the dialysis start and end times were not consistent on both PK days. Therefore, a representative metabolite PK profile could not be generated.
Time to Reach Cmax (Tmax) and Apparent Terminal Half-life (t1/2) of Dapro [Pre-dose on Day 1; 6-10 hours, 7-11 hours, 8-12 hours, 9-13 hours post dose on Day 15; pre-dose and 1, 2, 3 hours post-dose on Day 29]
Blood samples were collected at indicated time points for PK analysis of dapro. The data from each PK sampling day was combined to generate a single profile, and normalized to a 24-hour period to create a "Day 1" profile for NCA. Metabolite plasma concentrations were analyzed but PK parameters could not be calculated as the metabolites were partially eliminated through dialysis and the dialysis start and end times were not consistent on both PK days. Therefore, a representative metabolite PK profile could not be generated. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).
Number of Participants Who Discontinued Study Treatment [Up to Day 43]
Reasons of study treatment discontinuation included adverse events (AEs), protocol deviation, participants reached protocol defined stopping criteria, physician decision and withdrawal by participants. Number of participants who discontinued study treatment are presented. Analysis was performed on Safety Population which comprised of all participants who received at least one dose of study treatment.
Number of Participants With AEs and Serious Adverse Events (SAEs) [Up to Day 43]
An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability, is a congenital anomaly/ birth effect, other situations and is associated with liver injury or impaired liver function.
Sodium, Potassium, Glucose, Calcium, Phosphate Levels in Blood at Indicated Time Points [Up to Day 43]
Serum sodium, potassium, glucose, corrected calcium and phosphate levels were assessed as a clinical chemistry laboratory parameter from Baseline up to follow up visit at Day 43. Day 1 values were considered as Baseline values. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).
Albumin and Protein Levels in Blood at Indicated Tme Points [Up to Day 43]
Serum albumin and protein levels were assessed as a clinical chemistry laboratory parameter from Baseline up to follow up visit at Day 43. Day 1 values were considered as Baseline values. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).
Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Alkaline Phosphatase (Alk. Phosph) Levels in Blood at Indicated Time Points [Up to Day 43]
Serum ALT, AST and alk. phosph. levels were assessed as a clinical chemistry laboratory parameter from Baseline up to follow up visit at Day 43. Day 1 values were considered as Baseline values. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).
Bilirubin, Direct Bilirubin and Indirect Bilirubin Levels in Blood at Indicated Time Points [Up to Day 43]
Serum bilirubin, direct bilirubin and indirect bilirubin levels were assessed as a clinical chemistry laboratory parameter from Baseline up to follow up visit at Day 43. Day 1 values were considered as Baseline values. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).
Change From Baseline in Sodium, Potassium, Glucose, Calcium and Phosphate Levels [Baseline and up to Day 43]
Blood samples were collected from participants to evaluate clinical chemistry parameters including sodium, potassium, glucose, calcium and phosphate. Change from Baseline in clinical chemistry parameters at Day 15, Day 29 and Day 43 are presented. Day 1 values were considered as Baseline values. Change from Baseline was calculated by subtracting post-Baseline visit values minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Change From Baseline in Albumin and Protein Levels [Baseline and up to Day 43]
Blood samples were collected from participants to evaluate clinical chemistry parameters including albumin and protein. Change from Baseline in clinical chemistry parameters at Day 15, Day 29 and Day 43 are presented. Day 1 values were considered as Baseline values. Change from Baseline was calculated by subtracting post-Baseline visit values minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Change From Baseline in ALT, AST, Alk. Phosph. Levels [Baseline and up to Day 43]
Blood samples were collected from participants to evaluate clinical chemistry parameters including ALT, AST, Alk. phosph. Change from Baseline in clinical chemistry parameters at Day 15, Day 29 and Day 43 are presented. Day 1 values were considered as Baseline values. Change from Baseline was calculated by subtracting post-Baseline visit values minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Change From Baseline in Bilirubin, Direct Bilirubin, Indirect Bilirubin Levels [Baseline and up to Day 43]
Blood samples were collected from participants to evaluate clinical chemistry parameters including bilirubin, direct bilirubin and indirect bilirubin. Change from Baseline in clinical chemistry parameters at Day 15, Day 29 and Day 43 are presented. Day 1 values were considered as Baseline values. Change from Baseline was calculated by subtracting post-Baseline visit values minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points [Up to Day 43]
Serum leukocytes, neutrophils, basophils, eosinophils, lymphocytes, monocytes and platelet levels were assessed as a clinical hematology laboratory parameter from Baseline up to follow up visit at Day 43. Day 1 values were considered as Baseline values. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).
Mean Corpuscular Hemoglobin (MCH) Levels in Blood at Indicated Time Points [Up to Day 43]
Serum MCH levels were assessed as a clinical hematology laboratory parameter from Baseline up to follow up visit at Day 43. Day 1 values were considered as Baseline values. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).
Mean Corpuscular Hemoglobin Concentration (MCHC) Levels in Blood at Indicated Time Points [Up to Day 43]
Serum MCHC levels were assessed as a clinical hematology laboratory parameter from Baseline up to follow up visit at Day 43. Day 1 values were considered as Baseline values. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).
Mean Corpuscular Volume (MCV) Levels in Blood at Indicated Time Points [Up to Day 43]
Serum MCV levels were assessed as a clinical hematology laboratory parameter from Baseline up to follow up visit at Day 43. Day 1 values were considered as Baseline values. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).
Erythrocyte Distribution Width Levels in Blood at Indicated Time Points [Up to Day 43]
Erythrocyte distribution width levels were assessed as a clinical hematology laboratory parameter from Baseline up to follow up visit at Day 43. Day 1 values were considered as Baseline values. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).
Change From Baseline in MCH Levels [Baseline and up to Day 43]
Blood samples were collected from participants to evaluate clinical hematology parameters including MCH. Change from Baseline in clinical hematology parameters at Day 15, Day 29, Day 43 are presented. Day 1 values were considered as Baseline values. Change from Baseline was calculated by subtracting post-Baseline visit values minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Change From Baseline in MCHC Levels [Baseline and up to Day 43]
Blood samples were collected from participants to evaluate clinical hematology parameters including MCHC. Change from Baseline in clinical hematology parameters at Day 15, Day 29, Day 43 are presented. Day 1 values were considered as Baseline values. Change from Baseline was calculated by subtracting post-Baseline visit values minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Change From Baseline in MCV Levels [Baseline and up to Day 43]
Blood samples were collected from participants to evaluate clinical hematology parameters including MCV. Change from Baseline in clinical hematology parameters at Day 15, Day 29, Day 43 are presented. Day 1 values were considered as Baseline values. Change from Baseline was calculated by subtracting post-Baseline visit values minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Change From Baseline in Erythrocyte Distribution Width Levels [Baseline and up to Day 43]
Blood samples were collected from participants to evaluate clinical hematology parameters including erythrocyte distribution width. Change from Baseline in clinical hematology parameters at Day 15, Day 29, Day 43 are presented. Day 1 values were considered as Baseline values. Change from Baseline was calculated by subtracting post-Baseline visit values minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Change From Baseline in Leukocytes, Neutrophils, Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets Levels [Baseline and up to Day 43]
Blood samples were collected from participants to evaluate clinical hematology parameters including leukocytes, neutrophils, basophils, eosinophils, lymphocytes, monocytes, platelets. Change from Baseline in clinical hematology parameters at Day 15, Day 29, Day 43 are presented. Day 1 values were considered as Baseline values. Change from Baseline was calculated by subtracting post-Baseline visit values minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Number of Participants With Abnormal Electrocardiogram (ECG) Findings at Indicated Time Points [Up to Day 29]
Single measurements of 12-lead ECG were obtained in supine position using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT interval. Number of participants who had abnormal non clinically significant (NCS) and abnormal clinically significant (CS) ECG findings at Baseline (Week -4) and Day 29 are presented.
Change From Baseline in ECG Mean Heart Rate [Baseline and Day 29]
Single measurements of 12-lead ECG were obtained in supine position using an ECG machine to measure HR. Week -4 values were considered as Baseline values. Change from Baseline was calculated by subtracting post-Baseline visit values at Day 29 minus Baseline value.
Change From Baseline in ECG Parameters Including PR Interval, QRS Duration, QT Interval and QTcB [Baseline and Day 29]
Single measurements of 12-lead ECG were obtained in supine position using an ECG machine to measure PR interval, QRS duration, QT interval and QTcB. Week -4 values were considered as Baseline values. Change from Baseline was calculated by subtracting post-Baseline visit values at Day 29 minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Pre-dialysis and Post-dialysis [Up to Day 43]
Vital sign measurements including SBP and DBP were taken in a seated or semi-supine position in the dialysis chair at specific time points. SBP and DBP were measured pre-dialysis and post-dialysis. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Pulse Rate Values at Pre-dialysis and Post-dialysis [Up to Day 43]
Vital sign measurements including pulse rate values were taken in a seated or semi-supine position in the dialysis chair. Pulse rate was measured pre-dialysis and post-dialysis. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Weight Values at Post-dialysis [Up to Day 43]
Vital sign measurements including weight values were taken in a seated or semi-supine position in the dialysis chair. Weight was measured post-dialysis. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Change From Baseline in SBP and DBP Values at Pre-dialysis and Post-dialysis [Up to Day 43]
Vital sign measurements including SBP and DBP were taken in a seated or semi-supine position in the dialysis chair. SBP and DBP were measured pre-dialysis and post-dialysis. Pre-dialysis Baseline value was defined as SBP and DBP value obtained pre-dialysis on Day 1. Post-dialysis Baseline value was defined as SBP and DBP value obtained post-dialysis at Week -2. Change from Baseline was calculated by subtracting post-Baseline visit values minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Change From Baseline in Pulse Rate Value at Pre-dialysis and Post-dialysis [Up to Day 43]
Vital sign measurements including pulse rate were taken in a seated or semi-supine position in the dialysis chair. Pulse rate was measured pre-dialysis and post-dialysis. Pre-dialysis Baseline value was defined as pulse rate value obtained pre-dialysis on Day 1. Post-dialysis Baseline value was defined as pulse rate value obtained post-dialysis at Week -2. Change from Baseline was calculated by subtracting post-Baseline visit values minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Change From Baseline in Weight at Post-dialysis [Up to Day 43]
Vital sign measurements including weight were taken in a seated or semi-supine position in the dialysis chair. Weight was measured post-dialysis. Post-dialysis Baseline value was defined as SBP and DBP value obtained post-dialysis at Week -2. Change from Baseline was calculated by subtracting post-Baseline visit values minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

More than or equal to 18 years of age, at the time of signing the informed consent.
Hemoglobin: Stable Hemoglobin 9.0 - 11.5 gram per deciliter (g/dL).
Dialysis frequency: On hemodialysis (HD, hemofiltration or hemodiafiltration) three to five times weekly for at least 4 weeks prior to Day -28 Screening through Day 29.
Dialysis adequacy: A single pool Kt/Vurea of >=1.2 based on a historical value obtained within the prior three months 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 (URR) of at least 65 percent. NOTE: Only needs confirming at Day -28.
Erythropoiesis-stimulating agent (ESA)dose: Treated with the same ESA (epoetins or their biosimilars, or darbepoetin or methoxy polyethylene glycol [PEG]-epoetin beta) with total weekly dose varying by no more than 50 percent during the 4 weeks prior to Day -28.
Iron replacement therapy: Subjects may be on stable maintenance oral or intravenous (IV) (<=100 milligram (mg)/week) iron supplementation. If subjects are on oral or IV iron, then doses must be stable for the 4 weeks prior to Day -28, during the screening phase, and through the 29 days of treatment.
Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the consent form and in study protocol.

Exclusion Criteria:

Dialysis modality: Planned change from HD to peritoneal dialysis within the study time period.
Renal transplant: Planned for living-related kidney transplant.
High ESA dose: An epoetin dose of >=360 international unit (IU)/kilogram (kg)/week IV or >=250 IU/kg/week subcutaneous (SC) or darbepoetin dose of >=1.8 microgram (mcg)/kg/week IV or SC or methoxy PEG-epoetin beta dose of >= 2.2 mcg/kg/week within the prior 8 weeks through Day 1 (randomization).
Administration of methoxy PEG-epoetin beta within the prior 4 weeks through Day 1 (randomization).
Myocardial infarction or acute coronary syndrome: Within the 8 weeks prior to Screening through Day 1 (randomization).
Stroke or transient ischemic attack: Within 8 weeks prior to Screening though Day 1 (randomization).
Heart failure: Class IV heart failure, as defined by the New York Heart Association (NYHA) functional classification system diagnosed prior to Screening through Day 1 (randomization).
Correction of Q-T Interval using Bazett's formula (QTcB): QTcB >500 millisecond (msec) or QTcB >530 msec in subjects with Bundle Branch Block. There is no correction of Q-T Interval (QTc) exclusion for subjects with a predominantly paced rhythm.
Inflammatory disease: Active chronic inflammatory disease that could impact erythropoiesis (e.g., scleroderma, systemic lupus erythematosis, rheumatoid arthritis, celiac disease) diagnosed prior to Screening through Day 1 (randomization).
Hematological disease: Any hematological disease including those affecting platelets, white or red blood cells (e.g., sickle cell anemia, myelodysplastic syndromes, hematological malignancy, myeloma, hemolytic anemia and thalassemia), coagulation disorders (e.g., antiphospholipid syndrome, Protein C or S deficiency), or any other cause of anemia of chronic disease other than renal disease diagnosed prior to Screening though Day 1 (randomization).
Liver disease: Current liver disease, known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones) or evidence at Screening of abnormal liver function tests [alanine transaminase (ALT) or aspartate transaminase (AST) >2x upper limit of normal (ULN) or total bilirubin >1.5xULN]; or other hepatic abnormalities that in the opinion of the investigator would preclude the subject from participating in the study.

NOTE: Those with Hepatitis B or Hepatitis C are eligible provided these exclusions are not met.

Major surgery: Major surgery (excluding vascular access surgery) within the 8 weeks prior to Screening, during the Screening phase, or planned during the study.
Transfusion: Blood transfusion within the 8 weeks prior to Screening, during the Screening phase or an anticipated need for blood transfusion during the study.
Gastrointestinal (GI) Bleeding: Evidence of actively bleeding peptic, duodenal, or esophageal ulcer disease OR clinically significant GI bleeding within the 8 weeks prior to Screening through Day 1 (randomization).
Acute Infection: Clinical evidence of acute infection or history of infection requiring IV antibiotic therapy within the 4 weeks prior to Screening through Day 1 (randomization). NOTE: IV antibiotics as prophylaxis are allowed.
Malignancy: History of malignancy within the two years prior to randomization or currently receiving treatment for cancer, or has a known >=4 centimeter complex kidney cyst (i.e. Bosniak Category II F, III of IV). NOTE: ONLY exception is squamous cell or basal cell carcinoma of the skin that has been definitively treated >=8 weeks prior to Screening.
Severe allergic reactions: History of severe allergic or anaphylactic reactions or hypersensitivity to excipients in the investigational product
Drugs and supplements: Use of any prescription or non-prescription drugs or dietary supplements that are prohibited (as per protocol) from Screening until the Follow-up Visit.
Prior investigational product exposure: The Subject has participated in a clinical trial and has received an experimental investigational product within the prior 30 days from Screening through Day 1 (randomization).
Other conditions: Any other condition, clinical or laboratory abnormality, or examination finding that the investigator considers would put the subject at unacceptable risk, which may affect study compliance or prevent understanding of the aims or investigational procedures or possible consequences of the study.
Females ONLY: A female subject is not eligible to participate if she is pregnant [as confirmed by a positive serum human chorionic gonadotrophin (hCG) test for females of reproductive potential (FRP) only], breastfeeding, and if of reproductive potential does not agree to follow one of the options listed in the GSK Modified List of Highly Effective Methods for Avoiding Pregnancy in FRP.
Vitamin B12: At or below the lower limit of the reference range (may rescreen in a minimum of 8 weeks).
Folate: <2.0 nanogram (ng) per millilitre (mL) (4.5 nanomole/liter [L]) (may rescreen in a minimum of 4 weeks).
Ferritin: <100 ng/mL (<100 mcg/L).
Transferrin saturation (TSAT): <20 percent.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Northridge	California	United States	91324
2	GSK Investigational Site	San Dimas	California	United States	91773
3	GSK Investigational Site	Pembroke Pines	Florida	United States	33028
4	GSK Investigational Site	Greenbelt	Maryland	United States	20770
5	GSK Investigational Site	Roseville	Michigan	United States	48066
6	GSK Investigational Site	Kansas City	Missouri	United States	64111
7	GSK Investigational Site	Bronx	New York	United States	10461
8	GSK Investigational Site	Calgary	Alberta	Canada	T2R 0X7
9	GSK Investigational Site	Ottawa	Ontario	Canada	K1H 7W9
10	GSK Investigational Site	Toronto	Ontario	Canada	M3M 0B2
11	GSK Investigational Site	Greenfield Park	Quebec	Canada	J4V 2H1
12	GSK Investigational Site	Stuttgart	Baden-Wuerttemberg	Germany	70376
13	GSK Investigational Site	Villingen-Schwenningen	Baden-Wuerttemberg	Germany	78054
14	GSK Investigational Site	Kiel	Schleswig-Holstein	Germany	24105
15	GSK Investigational Site	Darmstadt		Germany	64295
16	GSK Investigational Site	Krasnodar		Russian Federation	350029
17	GSK Investigational Site	Moscow		Russian Federation	129327
18	GSK Investigational Site	Mytischi		Russian Federation	141009
19	GSK Investigational Site	Omsk		Russian Federation	644112
20	GSK Investigational Site	Penza		Russian Federation	440034
21	GSK Investigational Site	St-Petersburg		Russian Federation	197110
22	GSK Investigational Site	St. Petersburg		Russian Federation	194354
23	GSK Investigational Site	Yaroslavl		Russian Federation	150062
24	GSK Investigational Site	Almería		Spain	04009
25	GSK Investigational Site	Badalona		Spain	08916
26	GSK Investigational Site	Barcelona		Spain	08003
27	GSK Investigational Site	Granollers, Barcelona		Spain	08041
28	GSK Investigational Site	L'Hospitalet de Llobregat		Spain	08907
29	GSK Investigational Site	Lleida		Spain	25198
30	GSK Investigational Site	Madrid		Spain	28040
31	GSK Investigational Site	Madrid		Spain	28041
32	GSK Investigational Site	Madrid		Spain	28100
33	GSK Investigational Site	Malaga		Spain	29010
34	GSK Investigational Site	Manises (Valencia)		Spain	46940
35	GSK Investigational Site	San Sebastian de los Reyes		Spain	28702
36	GSK Investigational Site	Santander		Spain	39008
37	GSK Investigational Site	Santiago de Compostela		Spain	15706
38	GSK Investigational Site	Valladolid		Spain	47005

Sponsors and Collaborators

GlaxoSmithKline

Investigators

Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

More Information

Publications

Bailey CK, Caltabiano S, Cobitz AR, Huang C, Mahar KM, Patel VV. A randomized, 29-day, dose-ranging, efficacy and safety study of daprodustat, administered three times weekly in patients with anemia on hemodialysis. BMC Nephrol. 2019 Oct 16;20(1):372. doi: 10.1186/s12882-019-1547-z.

Responsible Party:

GlaxoSmithKline

ClinicalTrials.gov Identifier:

NCT02689206

Other Study ID Numbers:

204836
2015-004790-32

First Posted:

Feb 23, 2016

Last Update Posted:

Feb 25, 2020

Last Verified:

Feb 1, 2020

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Keywords provided by GlaxoSmithKline

Chronic kidney disease

Efficacy

Erythropoiesis-stimulating agent

GSK1278863

Safety

Hemodialysis-dependent anemia

Pharmacokinetics

Additional relevant MeSH terms:

Kidney Diseases

Renal Insufficiency, Chronic

Anemia

Glycine

Study Results

Participant Flow

Recruitment Details	Participants on Hemodialysis (HD) with anemia associated with chronic kidney disease (CKD) switching from Erythropoiesis-Stimulating Agent (ESA) treatment were recruited in this randomized, dose-ranging study. Participants with hemoglobin (Hgb) values between 9.0- 11.5 grams per deciliter (g/dL) were considered as eligible for recruitment.
Pre-assignment Detail	A total of 211 participants were screened; of which 108 were screen failures and 103 were randomized to receive at least one dose of either placebo or 10, 15, 25 or 30 milligrams (mg) of daprodustat (dapro). One participant who was randomized to the placebo group, erroneously received 25 mg dapro treatment throughout the 29-day treatment period

Arm/Group Title	Placebo	Dapro 10 mg	Dapro 15 mg	Dapro 25 mg	Dapro 30 mg
Arm/Group Description	Randomized participants received placebo tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 10 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 15 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 25 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 30 mg tablet via oral route three times weekly for 29 days
Period Title: Overall Study
STARTED	20	20	20	21	22
COMPLETED	17	19	16	17	14
NOT COMPLETED	3	1	4	4	8

Baseline Characteristics

Arm/Group Title	Placebo	Dapro 10 mg	Dapro 15 mg	Dapro 25 mg	Dapro 30 mg	Total
Arm/Group Description	Randomized participants received placebo tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 10 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 15 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 25 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 30 mg tablet via oral route three times weekly for 29 days	Total of all reporting groups
Overall Participants	20	20	20	21	22	103
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	61.0 (13.06)	63.6 (16.98)	59.5 (12.26)	67.2 (15.22)	65.4 (13.97)	63.4 (14.39)
Sex: Female, Male (Count of Participants)
Female	11 55%	8 40%	6 30%	9 42.9%	8 36.4%	42 40.8%
Male	9 45%	12 60%	14 70%	12 57.1%	14 63.6%	61 59.2%
Race/Ethnicity, Customized (Count of Participants)
African American/African Heritage	6 30%	6 30%	7 35%	5 23.8%	6 27.3%	30 29.1%
American Indian Or Alaskan Native	0 0%	1 5%	0 0%	0 0%	1 4.5%	2 1.9%
Asian - Central/South Asian Heritage	0 0%	1 5%	1 5%	0 0%	0 0%	2 1.9%
Native Hawaiian Or Other Pacific Islander	0 0%	0 0%	0 0%	1 4.8%	0 0%	1 1%
White- Arabic/North African Heritage	0 0%	0 0%	0 0%	1 4.8%	0 0%	1 1%
White-White/Caucasian/European Heritage	14 70%	12 60%	12 60%	14 66.7%	15 68.2%	67 65%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Hgb Levels at Day 29
Description	Blood samples were collected from participants for measurement of Hgb values. Baseline is the average of Hgb measured at Week -2 and Day 1 visits. Change from Baseline at Day 29 was defined as post dose value at Day 29 minus Baseline value. The analysis was performed on intent-to-treat (ITT) Population which comprised of all randomized participants who received at least one dose of study treatment, had a Baseline and at least one corresponding on treatment assessment, including Hgb.
Time Frame	Baseline and Day 29

Outcome Measure Data

Analysis Population Description
ITT Population

Arm/Group Title	Placebo	Dapro 10 mg	Dapro 15 mg	Dapro 25 mg	Dapro 30 mg
Arm/Group Description	Randomized participants received placebo tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 10 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 15 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 25 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 30 mg tablet via oral route three times weekly for 29 days
Measure Participants	17	19	16	17	15
Mean (Standard Deviation) [g/dL]	-0.61 (0.646)	-0.19 (1.750)	-0.13 (1.088)	0.64 (1.453)	0.55 (1.167)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dapro 10 mg
	Comments
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.57
	Confidence Interval	(2-Sided) 95% -0.31 to 1.45
	Parameter Dispersion	Type: Value:
	Estimation Comments	Analysis using a Repeated Measures Model with terms included for baseline, treatment, time and treatment*time. Model-adjusted treatment difference of dapro 10 mg arm from Placebo along with 95 percent CI are presented.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dapro 15 mg
	Comments
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.51
	Confidence Interval	(2-Sided) 95% -0.40 to 1.42
	Parameter Dispersion	Type: Value:
	Estimation Comments	Analysis using a Repeated Measures Model with terms included for baseline, treatment, time and treatment*time. Model-adjusted treatment difference of dapro 15 mg arm from Placebo along with 95 percent CI are presented.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dapro 25 mg
	Comments
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	1.47
	Confidence Interval	(2-Sided) 95% 0.59 to 2.35
	Parameter Dispersion	Type: Value:
	Estimation Comments	Analysis using a Repeated Measures Model with terms included for baseline, treatment, time and treatment*time. Model-adjusted treatment difference of dapro 25 mg arm from Placebo along with 95 percent CI are presented.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dapro 30 mg
	Comments
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	1.67
	Confidence Interval	(2-Sided) 95% 0.77 to 2.57
	Parameter Dispersion	Type: Value:
	Estimation Comments	Analysis using a Repeated Measures Model with terms included for baseline, treatment, time and treatment*time. Model-adjusted treatment difference of dapro 30 mg arm from Placebo along with 95 percent CI are presented.

2. Secondary Outcome

Title	Maximum Observed Change From Baseline in Plasma Erythropoietin (EPO)
Description	Blood samples were collected at Day 1, Day 15 and Day 29 for pharmacodynamic analysis of effect of dapro three times weekly dose regimens on EPO. Day 1 values were considered as Baseline values. Change from Baseline was calculated by subtracting post-Baseline visit values minus Baseline value. The change from Baseline at each given post-Baseline time point was calculated and the maximum change from Baseline was determined.
Time Frame	Baseline and up to Day 29

Outcome Measure Data

Analysis Population Description
ITT Population

Arm/Group Title	Placebo	Dapro 10 mg	Dapro 15 mg	Dapro 25 mg	Dapro 30 mg
Arm/Group Description	Randomized participants received placebo tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 10 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 15 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 25 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 30 mg tablet via oral route three times weekly for 29 days
Measure Participants	18	20	18	21	20
Mean (Standard Deviation) [International unit per liter (IU/L)]	53.761 (132.6875)	2.255 (84.8921)	73.369 (95.9772)	302.529 (469.8312)	477.644 (388.9757)

3. Secondary Outcome

Title	Maximum Observed Percent Change From Baseline in Vascular Endothelial Growth Factor (VEGF)
Description	Blood samples were collected at Day 1, Day 15 and Day 29 for pharmacodynamic analysis of effect of dapro three times weekly dose regimens on VEGF. Day 1 values were considered as Baseline values. The percent change from Baseline at each given post-Baseline time point was calculated (expressed as geometric mean) and the maximum percent change from Baseline was determined.
Time Frame	Baseline and up to Day 29

Outcome Measure Data

Analysis Population Description
ITT Population

Arm/Group Title	Placebo	Dapro 10 mg	Dapro 15 mg	Dapro 25 mg	Dapro 30 mg
Arm/Group Description	Randomized participants received placebo tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 10 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 15 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 25 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 30 mg tablet via oral route three times weekly for 29 days
Measure Participants	18	20	18	21	20
Geometric Mean (95% Confidence Interval) [Nanograms per liter (ng/L)]	20.35	43.75	32.16	53.34	76.09

4. Secondary Outcome

Title	Percent Change From Baseline in Hepcidin at Day 29
Description	Blood samples were collected at Day 1, Day 15 and Day 29 for pharmacodynamic analysis of effect of dapro three times weekly dose regimens on hepcidin. Day 1 values were considered as Baseline values. The Percent change from Baseline at Day 29 post-Baseline time point was calculated and expressed as geometric mean and the maximum change from Baseline was determined.
Time Frame	Baseline and Day 29

Outcome Measure Data

Analysis Population Description
ITT Population

Arm/Group Title	Placebo	Dapro 10 mg	Dapro 15 mg	Dapro 25 mg	Dapro 30 mg
Arm/Group Description	Randomized participants received placebo tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 10 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 15 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 25 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 30 mg tablet via oral route three times weekly for 29 days
Measure Participants	17	19	15	17	15
Geometric Mean (95% Confidence Interval) [Micrograms per liter (µg/L)]	27.81	35.37	3.83	-36.74	-36.09

5. Secondary Outcome

Title	Change From Baseline in Hematocrit Levels
Description	Blood samples were collected at Day 1, Day 15 and Day 29 for pharmacodynamic analysis of effect Dapro three times weekly dose regimens on hematocrit. Day 1 values were considered as Baseline values. Change from Baseline was calculated by subtracting post-dose visit values minus Baseline value. The change from Baseline at Day 29 post-Baseline time point was calculated.
Time Frame	Baseline and Day 29

Outcome Measure Data

Analysis Population Description
ITT Population

Arm/Group Title	Placebo	Dapro 10 mg	Dapro 15 mg	Dapro 25 mg	Dapro 30 mg
Arm/Group Description	Randomized participants received placebo tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 10 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 15 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 25 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 30 mg tablet via oral route three times weekly for 29 days
Measure Participants	16	19	14	16	15
Mean (Standard Deviation) [Proportion of red blood cells in blood]	-0.0218 (0.02469)	-0.0127 (0.05396)	-0.0149 (0.05379)	0.0150 (0.04511)	0.0215 (0.03852)

6. Secondary Outcome

Title	Change From Baseline in Red Blood Cell (RBC) Count
Description	Blood samples were collected at Day 1, Day 15 and Day 29 for pharmacodynamic analysis of effect Dapro three times weekly dose regimens on RBC count. Day 1 values were considered as Baseline values. Change from Baseline was calculated by subtracting post-dose visit values minus Baseline value. The change from Baseline at Day 29 post-Baseline time point was calculated.
Time Frame	Baseline and Day 29

Outcome Measure Data

Analysis Population Description
ITT Population

Arm/Group Title	Placebo	Dapro 10 mg	Dapro 15 mg	Dapro 25 mg	Dapro 30 mg
Arm/Group Description	Randomized participants received placebo tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 10 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 15 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 25 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 30 mg tablet via oral route three times weekly for 29 days
Measure Participants	16	19	14	16	15
Mean (Standard Deviation) [10^12 cells/L]	-0.19 (0.263)	-0.12 (0.494)	-0.13 (0.500)	0.12 (0.420)	0.15 (0.342)

7. Secondary Outcome

Title	Change From Baseline in Reticulocyte Count
Description	Blood samples were collected at Day 1, Day 15 and Day 29 for pharmacodynamic analysis of effect Dapro three times weekly dose regimens on reticulocyte count. Day 1 values were considered as Baseline values. Change from Baseline was calculated by subtracting post-Baseline visit values minus Baseline value. The change from Baseline at Day 29 post-Baseline time point was calculated.
Time Frame	Baseline and Day 29

Outcome Measure Data

Analysis Population Description
ITT Population

Arm/Group Title	Placebo	Dapro 10 mg	Dapro 15 mg	Dapro 25 mg	Dapro 30 mg
Arm/Group Description	Randomized participants received placebo tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 10 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 15 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 25 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 30 mg tablet via oral route three times weekly for 29 days
Measure Participants	16	18	14	16	15
Mean (Standard Deviation) [Percentage of reticulocyte]	-0.08 (0.848)	-0.11 (0.803)	-0.04 (0.581)	0.43 (0.547)	0.09 (0.695)

8. Secondary Outcome

Title	Change From Baseline in Reticulocyte Hemoglobin (CHr)
Description	Blood samples were collected at Day 1, Day 15 and Day 29 for pharmacodynamic analysis of effect Dapro three times weekly dose regimens on CHr. Day 1 values were considered as Baseline values. Change from Baseline was calculated by subtracting post-Baseline visit values minus Baseline value. The change from Baseline at Day 29 post-Baseline time point was calculated.
Time Frame	Baseline and Day 29

Outcome Measure Data

Analysis Population Description
ITT Population

Arm/Group Title	Placebo	Dapro 10 mg	Dapro 15 mg	Dapro 25 mg	Dapro 30 mg
Arm/Group Description	Randomized participants received placebo tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 10 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 15 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 25 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 30 mg tablet via oral route three times weekly for 29 days
Measure Participants	16	19	14	16	15
Mean (Standard Deviation) [Picograms (pg)]	-0.15 (1.375)	0.23 (1.335)	0.26 (1.103)	0.23 (1.040)	0.59 (1.436)

9. Secondary Outcome

Title	Area Under the Curve (AUC) From Time Zero to the Time of the Last Quantifiable Concentration (AUC[0-t]) and AUC From Time Zero to Infinity (AUC[0-inf]) of Dapro
Description	Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of dapro. The data from each PK sampling day was combined to generate a single profile, and normalized to a 24-hour period to create a "Day 1" profile for non-compartmental analysis (NCA). Metabolite plasma concentrations were analyzed but PK parameters could not be calculated as the metabolites were partially eliminated through dialysis and the dialysis start and end times were not consistent on both PK days. Therefore, a representative metabolite PK profile could not be generated. The analysis was performed on PK Population, which comprised of all participants from whom a PK sample has been obtained and analyzed. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).
Time Frame	Pre-dose on Day 1; 6-10 hours, 7-11 hours, 8-12 hours, 9-13 hours post dose on Day 15; pre-dose and 1, 2, 3 hours post-dose on Day 29

Outcome Measure Data

Analysis Population Description
PK Population. One participant who was randomized to the placebo group, erroneously received 25mg daprodustat treatment throughout the 29-day treatment period. This subject is counted within the daprodustat 25mg treatment group for all PK population and safety population analyses.

Arm/Group Title	Dapro 10 mg	Dapro 15 mg	Dapro 25 mg	Dapro 30 mg
Arm/Group Description	Randomized participants received dapro 10 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 15 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 25 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 30 mg tablet via oral route three times weekly for 29 days
Measure Participants	20	20	22	22
AUC (0-t); n= 19, 15, 16, 14	311.7 (91.4)	416.7 (168.6)	513.9 (396.1)	1010 (92.3)
AUC (0-inf); n= 12, 9, 8, 11	348.2 (78.2)	383.5 (142.7)	1214 (41.6)	1369 (59.3)

10. Secondary Outcome

Title	Maximum Observed Concentration of Dapro in Plasma (Cmax)
Description	Blood samples were collected at indicated time points for PK analysis of dapro. The data from each PK sampling day was combined to generate a single profile, and normalized to a 24-hour period to create a "Day 1" profile for NCA. Metabolite plasma concentrations were analyzed but PK parameters could not be calculated as the metabolites were partially eliminated through dialysis and the dialysis start and end times were not consistent on both PK days. Therefore, a representative metabolite PK profile could not be generated.
Time Frame	Pre-dose on Day 1; 6-10 hours, 7-11 hours, 8-12 hours, 9-13 hours post dose on Day 15; pre-dose and 1, 2, 3 hours post-dose on Day 29

Outcome Measure Data

Analysis Population Description
PK Population

Arm/Group Title	Dapro 10 mg	Dapro 15 mg	Dapro 25 mg	Dapro 30 mg
Arm/Group Description	Randomized participants received dapro 10 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 15 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 25 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 30 mg tablet via oral route three times weekly for 29 days
Measure Participants	19	15	16	14
Geometric Mean (Geometric Coefficient of Variation) [ng/mL]	140.0 (104.0)	141.4 (248.8)	246.9 (311.5)	387.3 (99.4)

11. Secondary Outcome

Title	Time to Reach Cmax (Tmax) and Apparent Terminal Half-life (t1/2) of Dapro
Description	Blood samples were collected at indicated time points for PK analysis of dapro. The data from each PK sampling day was combined to generate a single profile, and normalized to a 24-hour period to create a "Day 1" profile for NCA. Metabolite plasma concentrations were analyzed but PK parameters could not be calculated as the metabolites were partially eliminated through dialysis and the dialysis start and end times were not consistent on both PK days. Therefore, a representative metabolite PK profile could not be generated. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).
Time Frame	Pre-dose on Day 1; 6-10 hours, 7-11 hours, 8-12 hours, 9-13 hours post dose on Day 15; pre-dose and 1, 2, 3 hours post-dose on Day 29

Outcome Measure Data

Analysis Population Description
PK Population. One participant who was randomized to the placebo group, erroneously received 25mg daprodustat treatment throughout the 29-day treatment period. This subject is counted within the daprodustat 25mg treatment group for all PK population and safety population analyses.

Arm/Group Title	Dapro 10 mg	Dapro 15 mg	Dapro 25 mg	Dapro 30 mg
Arm/Group Description	Randomized participants received dapro 10 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 15 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 25 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 30 mg tablet via oral route three times weekly for 29 days
Measure Participants	20	20	22	22
Tmax; n= 19, 15, 16, 14	2.456 (78.9)	2.106 (82.1)	2.297 (96.5)	1.718 (58.0)
T1/2; n= 12, 9, 8, 11	2.086 (50.0)	1.886 (62.3)	1.418 (58.4)	2.897 (38.7)

12. Secondary Outcome

Title	Number of Participants Who Discontinued Study Treatment
Description	Reasons of study treatment discontinuation included adverse events (AEs), protocol deviation, participants reached protocol defined stopping criteria, physician decision and withdrawal by participants. Number of participants who discontinued study treatment are presented. Analysis was performed on Safety Population which comprised of all participants who received at least one dose of study treatment.
Time Frame	Up to Day 43

Outcome Measure Data

Analysis Population Description
Safety Population. One participant who was randomized to the placebo group, erroneously received 25mg daprodustat treatment throughout the 29-day treatment period. This subject is counted within the daprodustat 25mg treatment group for all PK population and safety population analyses.

Arm/Group Title	Placebo	Dapro 10 mg	Dapro 15 mg	Dapro 25 mg	Dapro 30 mg
Arm/Group Description	Randomized participants received placebo tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 10 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 15 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 25 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 30 mg tablet via oral route three times weekly for 29 days
Measure Participants	19	20	20	22	22
AEs	0 0%	0 0%	1 5%	0 0%	1 4.5%
Protocol deviation	1 5%	0 0%	0 0%	1 4.8%	2 9.1%
Participant reached stopping criteria	0 0%	1 5%	2 10%	3 14.3%	4 18.2%
Physician decision	1 5%	0 0%	0 0%	0 0%	0 0%
Withdrawal by subject	1 5%	0 0%	1 5%	0 0%	0 0%

13. Secondary Outcome

Title	Number of Participants With AEs and Serious Adverse Events (SAEs)
Description	An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability, is a congenital anomaly/ birth effect, other situations and is associated with liver injury or impaired liver function.
Time Frame	Up to Day 43

Outcome Measure Data

Analysis Population Description
Safety Population. One participant who was randomized to the placebo group, erroneously received 25mg daprodustat treatment throughout the 29-day treatment period. This subject is counted within the daprodustat 25mg treatment group for all PK population and safety population analyses.

Arm/Group Title	Placebo	Dapro 10 mg	Dapro 15 mg	Dapro 25 mg	Dapro 30 mg
Arm/Group Description	Randomized participants received placebo tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 10 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 15 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 25 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 30 mg tablet via oral route three times weekly for 29 days
Measure Participants	19	20	20	22	22
Any AE	10 50%	10 50%	6 30%	7 33.3%	7 31.8%
Any SAE	4 20%	3 15%	2 10%	1 4.8%	3 13.6%

14. Secondary Outcome

Title	Sodium, Potassium, Glucose, Calcium, Phosphate Levels in Blood at Indicated Time Points
Description	Serum sodium, potassium, glucose, corrected calcium and phosphate levels were assessed as a clinical chemistry laboratory parameter from Baseline up to follow up visit at Day 43. Day 1 values were considered as Baseline values. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).
Time Frame	Up to Day 43

Outcome Measure Data

Analysis Population Description
Safety Population. One participant who was randomized to the placebo group, erroneously received 25mg daprodustat treatment throughout the 29-day treatment period. This subject is counted within the daprodustat 25mg treatment group for all PK population and safety population analyses.

Arm/Group Title	Placebo	Dapro 10 mg	Dapro 15 mg	Dapro 25 mg	Dapro 30 mg
Arm/Group Description	Randomized participants received placebo tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 10 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 15 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 25 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 30 mg tablet via oral route three times weekly for 29 days
Measure Participants	19	20	20	22	22
Sodium; Day 1; n= 18, 20, 20, 22, 22	138.8 (2.85)	138.1 (2.31)	138.7 (2.83)	139.4 (2.38)	138.4 (1.76)
Sodium; Day 15; n= 17, 20, 18, 22, 20	137.7 (3.16)	137.5 (2.72)	138.1 (1.60)	138.0 (2.36)	137.2 (1.74)
Sodium; Day 29; n= 17, 19, 18, 19, 17	137.8 (3.96)	136.8 (2.70)	137.9 (2.85)	138.8 (2.74)	137.1 (2.46)
Sodium; Day 43; n= 15, 20, 18, 21, 21	139.2 (2.88)	138.1 (1.77)	137.9 (2.37)	138.8 (2.02)	137.6 (1.88)
Potassium; Day 1; n= 18, 20, 20, 22, 22	4.68 (0.840)	4.73 (0.768)	4.64 (0.826)	4.79 (0.514)	4.83 (0.685)
Potassium; Day 15; n= 17, 20, 18, 22, 20	4.72 (0.763)	4.77 (0.542)	4.57 (0.635)	4.82 (0.765)	4.80 (0.791)
Potassium; Day 29; n= 17, 19, 18, 19, 17	4.78 (0.919)	4.87 (0.751)	4.57 (0.472)	4.86 (0.619)	4.96 (0.941)
Potassium; Day 43; n= 15, 20, 18, 21, 21	4.69 (0.951)	4.68 (0.562)	4.59 (0.657)	4.76 (0.752)	4.80 (0.946)
Glucose; Day 1; n= 18, 20, 20, 22, 22	6.66 (3.088)	6.66 (2.716)	6.41 (3.507)	7.05 (2.491)	8.95 (5.012)
Glucose; Day 15; n= 17, 20, 18, 22, 20	7.89 (3.425)	7.16 (2.844)	7.03 (3.236)	7.26 (2.852)	8.67 (4.198)
Glucose; Day 29; n= 17, 19, 18, 19, 17	8.21 (4.951)	7.49 (3.949)	7.21 (3.953)	7.77 (4.621)	8.75 (5.708)
Glucose; Day 43; n= 15, 20, 18, 21, 21	6.93 (3.126)	6.72 (2.965)	7.09 (3.533)	6.27 (1.958)	8.93 (4.280)
Calcium corrected; Day 1; n= 18, 20, 20, 22, 22	2.286 (0.2116)	2.270 (0.1244)	2.241 (0.1675)	2.219 (0.1589)	2.215 (0.1163)
Calcium corrected; Day 15; n= 17, 20, 18, 22, 20	2.261 (0.1698)	2.219 (0.1252)	2.213 (0.1723)	2.188 (0.1360)	2.203 (0.1111)
Calcium corrected; Day 29; n= 17, 19, 18, 19, 17	2.205 (0.1431)	2.248 (0.1352)	2.244 (0.1577)	2.198 (0.1343)	2.225 (0.1810)
Calcium corrected; Day 43; n= 15, 20, 18, 21, 21	2.251 (0.1582)	2.235 (0.1593)	2.271 (0.1823)	2.201 (0.1206)	2.256 (0.1473)
Phosphate; Day 1; n= 18, 20, 20, 22, 22	1.608 (0.5143)	1.528 (0.5557)	1.498 (0.5265)	1.318 (0.3647)	1.566 (0.4269)
Phosphate; Day 15; n= 17, 20, 18, 22, 20	1.621 (0.4221)	1.710 (0.3912)	1.642 (0.5021)	1.348 (0.3138)	1.645 (0.4785)
Phosphate; Day 29; n= 17, 19, 18, 19, 17	1.709 (0.5872)	1.592 (0.4121)	1.644 (0.5322)	1.453 (0.4489)	1.550 (0.3575)
Phosphate; Day 43; n= 15, 20, 18, 21, 21	1.550 (0.5828)	1.460 (0.4550)	1.472 (0.4240)	1.412 (0.4441)	1.398 (0.4718)

15. Secondary Outcome

Title	Albumin and Protein Levels in Blood at Indicated Tme Points
Description	Serum albumin and protein levels were assessed as a clinical chemistry laboratory parameter from Baseline up to follow up visit at Day 43. Day 1 values were considered as Baseline values. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).
Time Frame	Up to Day 43

Outcome Measure Data

Analysis Population Description
Safety Population. One participant who was randomized to the placebo group, erroneously received 25mg daprodustat treatment throughout the 29-day treatment period. This subject is counted within the daprodustat 25mg treatment group for all PK population and safety population analyses.

Arm/Group Title	Placebo	Dapro 10 mg	Dapro 15 mg	Dapro 25 mg	Dapro 30 mg
Arm/Group Description	Randomized participants received placebo tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 10 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 15 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 25 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 30 mg tablet via oral route three times weekly for 29 days
Measure Participants	19	20	20	22	22
Albumin; Day 1; n= 18, 20, 20, 22, 22	37.6 (2.89)	38.6 (2.46)	38.7 (3.84)	38.8 (2.22)	38.1 (3.52)
Albumin; Day 15; n= 17, 20, 18, 22, 20	38.1 (2.68)	38.1 (2.65)	38.4 (3.42)	38.4 (2.52)	37.2 (3.01)
Albumin; Day 29; n= 17, 19, 18, 19, 17	36.5 (3.22)	37.2 (3.26)	37.6 (3.62)	37.4 (2.17)	36.9 (4.15)
Albumin; Day 43; n= 15, 20, 18, 21, 21	37.1 (2.85)	38.1 (3.02)	37.9 (3.95)	39.0 (3.11)	37.5 (2.86)
Protein; Day 1; n= 18, 20 ,20, 22, 22	67.3 (4.90)	66.9 (5.42)	67.4 (4.89)	66.4 (5.16)	65.7 (4.65)
Protein; Day 15; n= 17, 20, 18, 22, 20	68.1 (4.87)	66.5 (4.88)	67.3 (4.28)	65.6 (5.13)	64.3 (4.70)
Protein; Day 29; n= 17, 19, 18, 19, 17	66.1 (4.52)	65.7 (4.75)	66.0 (4.51)	65.5 (6.50)	65.3 (5.30)
Protein; Day 43; n= 15, 20, 18, 21, 21	67.2 (4.25)	67.4 (5.14)	66.8 (4.02)	66.7 (7.70)	66.6 (6.34)

16. Secondary Outcome

Title	Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Alkaline Phosphatase (Alk. Phosph) Levels in Blood at Indicated Time Points
Description	Serum ALT, AST and alk. phosph. levels were assessed as a clinical chemistry laboratory parameter from Baseline up to follow up visit at Day 43. Day 1 values were considered as Baseline values. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).
Time Frame	Up to Day 43

Outcome Measure Data

Analysis Population Description
Safety Population One participant who was randomized to the placebo group, erroneously received 25mg daprodustat treatment throughout the 29-day treatment period. This subject is counted within the daprodustat 25mg treatment group for all PK population and safety population analyses.

Arm/Group Title	Placebo	Dapro 10 mg	Dapro 15 mg	Dapro 25 mg	Dapro 30 mg
Arm/Group Description	Randomized participants received placebo tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 10 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 15 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 25 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 30 mg tablet via oral route three times weekly for 29 days
Measure Participants	19	20	20	22	22
ALT; Day 1; n= 18, 20, 20, 22, 22	12.6 (9.36)	13.4 (7.51)	14.6 (11.39)	10.7 (5.75)	11.5 (5.94)
ALT; Day 15; n= 17, 20, 18, 22, 20	16.5 (13.80)	13.9 (10.58)	12.4 (7.87)	11.9 (6.58)	8.4 (2.11)
ALT; Day 29; n= 17, 19, 18, 19, 17	24.4 (32.34)	12.8 (6.43)	12.2 (6.40)	10.9 (5.67)	8.6 (3.12)
ALT; Day 43; n= 15, 20, 18, 21, 21	14.3 (8.55)	13.8 (8.03)	12.8 (6.89)	13.1 (5.19)	11.2 (5.57)
AST; Day 1; n= 18, 20, 20, 22, 22	14.9 (5.58)	14.2 (5.19)	17.2 (12.31)	14.4 (5.85)	13.6 (3.63)
AST; Day 15; n= 17, 20, 18, 22, 20	17.1 (7.30)	14.3 (5.67)	15.0 (7.72)	15.4 (6.33)	12.4 (2.89)
AST; Day 29; n= 17, 19, 18, 19, 17	26.8 (30.04)	13.8 (5.01)	16.0 (8.44)	15.0 (6.35)	13.5 (3.12)
AST; Day 43; n= 15, 20, 18, 21, 21	15.9 (6.65)	14.9 (6.07)	17.2 (11.40)	15.7 (6.31)	14.3 (4.76)
Alk. phosph; Day 1; n= 18, 20, 20, 22, 22	97.0 (33.07)	112.3 (74.61)	106.8 (84.85)	99.4 (47.26)	115.4 (72.35)
Alk. phosph; Day 15; n= 17, 20, 18, 22,20	102.4 (34.70)	115.4 (73.37)	114.5 (82.29)	101.5 (56.44)	110.0 (62.65)
Alk. phosph.; Day 29; n= 17, 19, 18, 19,17	94.1 (35.07)	120.2 (81.15)	109.2 (83.14)	93.5 (42.92)	120.4 (67.51)
Alk. phosph.; Day 43; n= 15, 20, 18, 21,21	96.5 (34.12)	117.6 (76.61)	113.8 (78.69)	116.2 (96.02)	108.6 (50.49)

17. Secondary Outcome

Title	Bilirubin, Direct Bilirubin and Indirect Bilirubin Levels in Blood at Indicated Time Points
Description	Serum bilirubin, direct bilirubin and indirect bilirubin levels were assessed as a clinical chemistry laboratory parameter from Baseline up to follow up visit at Day 43. Day 1 values were considered as Baseline values. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).
Time Frame	Up to Day 43

Outcome Measure Data

Analysis Population Description
Safety Population. One participant who was randomized to the placebo group, erroneously received 25mg daprodustat treatment throughout the 29-day treatment period. This subject is counted within the daprodustat 25mg treatment group for all PK population and safety population analyses.

Arm/Group Title	Placebo	Dapro 10 mg	Dapro 15 mg	Dapro 25 mg	Dapro 30 mg
Arm/Group Description	Randomized participants received placebo tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 10 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 15 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 25 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 30 mg tablet via oral route three times weekly for 29 days
Measure Participants	19	20	20	22	22
Bilirubin; Day 1; n= 18, 20, 20, 22, 22	6.6 (1.65)	7.8 (3.11)	6.6 (1.31)	6.5 (1.10)	7.2 (2.44)
Bilirubin; Day 15; n= 17, 20, 18, 22, 20	6.7 (3.08)	7.1 (2.29)	7.2 (2.67)	6.5 (1.10)	7.8 (2.24)
Bilirubin; Day 29; n= 17, 19, 18, 19, 17	6.8 (2.24)	6.9 (1.93)	7.6 (2.12)	6.5 (1.47)	7.8 (2.44)
Bilirubin; Day 43; n= 15, 20 ,18, 21, 21	6.0 (1.07)	7.0 (2.38)	7.2 (2.07)	6.5 (1.25)	7.5 (2.44)
Direct bilirubin; Day 1; n= 18, 20, 20, 22, 22	1.8 (1.17)	1.9 (0.79)	2.0 (1.12)	1.9 (0.75)	2.4 (1.33)
Direct bilirubin; Day 15; n= 17, 20, 18, 22, 20	1.5 (1.66)	2.2 (0.62)	2.4 (1.29)	1.8 (0.85)	2.6 (1.14)
Direct bilirubin; Day 29; n= 17, 19, 18, 19,17	2.5 (2.29)	1.6 (1.07)	2.7 (0.97)	1.8 (0.63)	2.4 (1.46)
Direct bilirubin; Day 43; n= 15, 20, 18, 21,21	1.3 (1.23)	1.9 (0.45)	2.3 (0.77)	1.7 (0.72)	2.3 (1.31)
Indirect bilirubin; Day 1; n= 18, 20, 20, 22, 22	4.8 (1.22)	5.9 (2.94)	4.6 (0.94)	4.6 (1.14)	4.8 (1.92)
Indirect bilirubin; Day 15; n= 17, 20, 18, 22, 20	5.2 (2.01)	4.9 (2.10)	4.8 (1.83)	4.7 (0.98)	5.2 (1.77)
Indirect bilirubin; Day 29; n= 17, 19, 18, 19, 17	4.4 (2.03)	5.4 (1.64)	4.9 (1.57)	4.7 (1.52)	5.4 (1.70)
Indirect bilirubin; Day 43; n= 15, 20, 18, 21, 21	4.7 (0.98)	5.1 (2.38)	4.9 (1.41)	4.8 (1.48)	5.2 (1.73)

18. Secondary Outcome

Title	Change From Baseline in Sodium, Potassium, Glucose, Calcium and Phosphate Levels
Description	Blood samples were collected from participants to evaluate clinical chemistry parameters including sodium, potassium, glucose, calcium and phosphate. Change from Baseline in clinical chemistry parameters at Day 15, Day 29 and Day 43 are presented. Day 1 values were considered as Baseline values. Change from Baseline was calculated by subtracting post-Baseline visit values minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Time Frame	Baseline and up to Day 43

Outcome Measure Data

Analysis Population Description
Safety Population. One participant who was randomized to the placebo group, erroneously received 25mg daprodustat treatment throughout the 29-day treatment period. This subject is counted within the daprodustat 25mg treatment group for all PK population and safety population analyses.

Arm/Group Title	Placebo	Dapro 10 mg	Dapro 15 mg	Dapro 25 mg	Dapro 30 mg
Arm/Group Description	Randomized participants received placebo tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 10 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 15 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 25 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 30 mg tablet via oral route three times weekly for 29 days
Measure Participants	19	20	20	22	22
Sodium; Day 15; n= 17, 20, 18, 22, 20	-0.9 (2.73)	-0.6 (2.62)	-0.5 (2.64)	-1.4 (2.06)	-1.0 (2.13)
Sodium; Day 29; n= 17, 19, 18, 19, 17	-1.1 (2.26)	-1.2 (3.08)	-0.9 (2.26)	-0.5 (2.82)	-1.2 (2.70)
Sodium; Day 43; n= 15, 20, 18, 21, 21	0.7 (2.06)	0.1 (2.35)	-0.6 (2.28)	-0.5 (2.60)	-0.6 (2.23)
Potassium; Day 15; n= 17, 20, 18, 22, 20	0.04 (0.462)	0.05 (0.526)	-0.09 (1.099)	0.03 (0.944)	-0.08 (0.635)
Potassium; Day 29; n= 17, 19, 18, 19, 17	0.20 (0.744)	0.05 (0.660)	-0.14 (0.651)	0.02 (0.640)	0.11 (0.673)
Potassium; Day 43; n= 15, 20, 18, 21, 21	0.04 (0.565)	-0.05 (0.674)	-0.06 (1.004)	-0.06 (0.579)	-0.02 (0.932)
Glucose; Day 15; n= 17, 20, 18, 22, 20	1.14 (3.339)	0.51 (2.959)	0.45 (1.740)	0.21 (1.620)	-0.03 (2.364)
Glucose; Day 29; n= 17, 19, 18, 19, 17	1.48 (3.771)	0.70 (3.756)	0.73 (1.135)	0.61 (4.188)	-0.36 (3.786)
Glucose; Day 43; n= 15, 20, 18, 21, 21	0.23 (1.335)	0.06 (3.072)	0.52 (1.383)	-0.81 (2.516)	-0.12 (3.619)
Calcium; Day 15; n= 17, 20, 18, 22, 20	-0.011 (0.1227)	-0.051 (0.1354)	-0.026 (0.1439)	-0.031 (0.0956)	-0.010 (0.0912)
Calcium; Day 29; n= 17, 19, 18, 19, 17	-0.054 (0.1486)	-0.025 (0.1129)	-0.009 (0.1556)	-0.012 (0.0939)	0.001 (0.1019)
Calcium; Day 43; n= 15, 20, 18, 21, 21	-0.015 (0.1576)	-0.035 (0.1261)	0.018 (0.1852)	0.001 (0.0742)	0.033 (0.1489)
Phosphate; Day 15; n= 17, 20, 18, 22, 20	-0.091 (0.4051)	0.183 (0.5184)	0.111 (0.5715)	0.030 (0.3268)	0.095 (0.3367)
Phosphate; Day 29; n= 17, 19, 18, 19, 17	0.091 (0.3882)	0.011 (0.4932)	0.069 (0.4950)	0.129 (0.2740)	-0.026 (0.3653)
Phosphate; Day 43; n= 15, 20, 18, 21, 21	-0.067 (0.4337)	-0.068 (0.5324)	-0.053 (0.5400)	0.102 (0.3433)	-0.117 (0.5117)

19. Secondary Outcome

Title	Change From Baseline in Albumin and Protein Levels
Description	Blood samples were collected from participants to evaluate clinical chemistry parameters including albumin and protein. Change from Baseline in clinical chemistry parameters at Day 15, Day 29 and Day 43 are presented. Day 1 values were considered as Baseline values. Change from Baseline was calculated by subtracting post-Baseline visit values minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Time Frame	Baseline and up to Day 43

Outcome Measure Data

Analysis Population Description
Safety Population. One participant who was randomized to the placebo group, erroneously received 25mg daprodustat treatment throughout the 29-day treatment period. This subject is counted within the daprodustat 25mg treatment group for all PK population and safety population analyses.

Arm/Group Title	Placebo	Dapro 10 mg	Dapro 15 mg	Dapro 25 mg	Dapro 30 mg
Arm/Group Description	Randomized participants received placebo tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 10 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 15 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 25 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 30 mg tablet via oral route three times weekly for 29 days
Measure Participants	19	20	20	22	22
Albumin; Day 15; n= 17, 20, 18, 22, 20	0.8 (1.60)	-0.5 (1.64)	0.2 (2.24)	-0.5 (1.44)	-1.0 (2.34)
Albumin; Day 29; n= 17, 19, 18, 19, 17	-0.5 (2.24)	-1.3 (2.03)	-0.7 (2.00)	-1.3 (1.85)	-0.9 (1.76)
Albumin; Day 43; n= 15, 20, 18, 21, 21	0.1 (2.00)	-0.6 (2.14)	-0.7 (2.22)	0.1 (3.85)	-0.3 (1.74)
Protein; Day 15; n= 17, 20, 18, 22, 20	0.8 (2.97)	-0.4 (3.25)	0.3 (3.65)	-0.7 (2.35)	-1.5 (3.03)
Protein; Day 29; n= 17, 19, 18, 19, 17	-1.1 (4.26)	-0.8 (3.82)	-1.2 (2.90)	-1.0 (3.28)	0.1 (2.56)
Protein; Day 43; n= 15, 20, 18, 21, 21	-0.1 (4.19)	0.6 (4.38)	-0.9 (3.17)	0.3 (4.84)	1.2 (3.95)

20. Secondary Outcome

Title	Change From Baseline in ALT, AST, Alk. Phosph. Levels
Description	Blood samples were collected from participants to evaluate clinical chemistry parameters including ALT, AST, Alk. phosph. Change from Baseline in clinical chemistry parameters at Day 15, Day 29 and Day 43 are presented. Day 1 values were considered as Baseline values. Change from Baseline was calculated by subtracting post-Baseline visit values minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Time Frame	Baseline and up to Day 43

Outcome Measure Data

Analysis Population Description
Safety Population. One participant who was randomized to the placebo group, erroneously received 25mg daprodustat treatment throughout the 29-day treatment period. This subject is counted within the daprodustat 25mg treatment group for all PK population and safety population analyses.

Arm/Group Title	Placebo	Dapro 10 mg	Dapro 15 mg	Dapro 25 mg	Dapro 30 mg
Arm/Group Description	Randomized participants received placebo tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 10 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 15 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 25 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 30 mg tablet via oral route three times weekly for 29 days
Measure Participants	19	20	20	22	22
ALT; Day 15; n= 17, 20, 18, 22, 20	3.6 (9.59)	0.5 (5.65)	-3.1 (5.53)	1.1 (4.79)	-3.4 (5.52)
ALT; Day 29; n= 17, 19, 18, 19, 17	11.8 (32.39)	-0.9 (4.65)	-3.4 (9.83)	-0.2 (3.87)	-3.6 (4.72)
ALT; Day 43; n= 15, 20, 18, 21, 21	0.9 (4.32)	0.4 (5.29)	-2.5 (8.97)	2.2 (4.08)	-0.4 (3.69)
AST; Day 15; n= 17, 20, 18, 22, 20	2.3 (5.70)	0.1 (2.45)	-2.7 (6.29)	1.0 (5.26)	-1.6 (3.32)
AST; Day 29; n= 17, 19, 18, 19, 17	11.5 (30.64)	-0.3 (3.30)	-1.8 (5.60)	0.9 (3.60)	-0.3 (3.67)
AST; Day 43; n= 15, 20, 18, 21, 21	0.6 (3.94)	0.7 (2.49)	-0.6 (7.99)	1.5 (3.71)	0.7 (3.41)
Alk.phosph.; Day 15; n= 17, 20, 18, 22, 20	3.2 (10.28)	3.2 (16.13)	2.7 (29.73)	2.1 (17.23)	-4.7 (18.90)
Alk.phosph.; Day 29; n= 17, 19, 18, 19, 17	-0.4 (19.31)	5.1 (19.09)	-0.9 (30.13)	0.9 (13.47)	-1.2 (28.60)
Alk.phosph.; Day 43; n= 15, 20, 18, 21, 21	-1.5 (17.01)	5.4 (21.34)	2.7 (31.96)	18.0 (66.44)	-8.4 (56.06)

21. Secondary Outcome

Title	Change From Baseline in Bilirubin, Direct Bilirubin, Indirect Bilirubin Levels
Description	Blood samples were collected from participants to evaluate clinical chemistry parameters including bilirubin, direct bilirubin and indirect bilirubin. Change from Baseline in clinical chemistry parameters at Day 15, Day 29 and Day 43 are presented. Day 1 values were considered as Baseline values. Change from Baseline was calculated by subtracting post-Baseline visit values minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Time Frame	Baseline and up to Day 43

Outcome Measure Data

Analysis Population Description
Safety Population. One participant who was randomized to the placebo group, erroneously received 25mg daprodustat treatment throughout the 29-day treatment period. This subject is counted within the Daprodustat 25mg treatment group for all PK population and safety population analyses.

Arm/Group Title	Placebo	Dapro 10 mg	Dapro 15 mg	Dapro 25 mg	Dapro 30 mg
Arm/Group Description	Randomized participants received placebo tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 10 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 15 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 25 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 30 mg tablet via oral route three times weekly for 29 days
Measure Participants	19	20	20	22	22
Bilirubin; Day 15; n= 17, 20, 18, 22, 20	0.2 (1.56)	-0.7 (1.49)	0.8 (2.07)	0.0 (1.38)	0.5 (1.93)
Bilirubin; Day 29; n= 17, 19, 18, 19, 17	0.2 (0.97)	-0.3 (1.20)	1.0 (1.41)	0.1 (1.56)	0.2 (0.97)
Bilirubin; Day 43; n= 15, 20, 18, 21, 21	-0.1 (0.52)	-0.8 (1.51)	0.6 (2.04)	0.1 (1.34)	0.4 (1.36)
Direct bilirubin; Day 15; n= 17, 20, 18, 22, 20	-0.1 (1.11)	0.3 (0.73)	0.6 (0.92)	-0.1 (0.97)	0.2 (1.11)
Direct bilirubin; Day 29; n= 17, 19, 18, 19, 17	0.7 (1.86)	-0.3 (1.00)	0.7 (0.97)	-0.1 (1.05)	-0.1 (1.50)
Direct bilirubin; Day 43; n= 15, 20, 18, 21, 21	-0.1 (1.19)	0.0 (0.92)	0.3 (1.03)	-0.2 (1.08)	-0.1 (1.34)
Indirect bilirubin; Day 15; n= 17, 20, 18, 22, 20	0.4 (1.46)	-1.0 (1.38)	0.2 (1.80)	0.1 (1.44)	0.3 (1.75)
Indirect bilirubin; Day 29; n= 17, 19, 18, 19, 17	-0.5 (1.66)	0.0 (1.15)	0.3 (1.71)	0.2 (1.62)	0.4 (1.46)
Indirect bilirubin; Day 43; n= 15, 20, 18, 21, 21	0.0 (1.07)	-0.8 (1.64)	0.2 (1.66)	0.3 (1.82)	0.5 (1.40)

22. Secondary Outcome

Title	Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points
Description	Serum leukocytes, neutrophils, basophils, eosinophils, lymphocytes, monocytes and platelet levels were assessed as a clinical hematology laboratory parameter from Baseline up to follow up visit at Day 43. Day 1 values were considered as Baseline values. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).
Time Frame	Up to Day 43

Outcome Measure Data

Analysis Population Description
Safety population. One participant who was randomized to the placebo group, erroneously received 25mg daprodustat treatment throughout the 29-day treatment period. This subject is counted within the daprodustat 25mg treatment group for all PK population and safety population analyses.

Arm/Group Title	Placebo	Dapro 10 mg	Dapro 15 mg	Dapro 25 mg	Dapro 30 mg
Arm/Group Description	Randomized participants received placebo tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 10 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 15 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 25 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 30 mg tablet via oral route three times weekly for 29 days
Measure Participants	19	20	20	22	22
Leukocytes; Day 1; n= 18, 19, 19, 20, 21	6.28 (1.750)	6.07 (1.601)	5.88 (1.510)	6.44 (1.595)	5.90 (1.825)
Leukocytes; Day 15; n= 17, 19, 17, 21, 21	7.01 (2.140)	5.85 (1.720)	6.21 (1.918)	6.52 (1.427)	5.87 (1.961)
Leukocytes; Day 29; n= 16, 19, 17, 18, 17	6.66 (1.707)	6.59 (1.890)	5.88 (1.685)	6.33 (1.820)	6.11 (2.574)
Leukocytes; Day 43; n= 16, 20, 19, 20, 19	7.05 (2.006)	7.25 (2.520)	6.00 (1.694)	6.77 (2.547)	6.42 (2.010)
Neutrophils; Day 1; n= 18, 19, 19, 20, 21	4.030 (1.6128)	4.097 (1.5763)	3.522 (1.3492)	3.954 (1.4097)	3.785 (1.5024)
Neutrophils; Day 15; n= 17, 19, 17, 21, 21	4.666 (1.8113)	3.887 (1.5659)	3.707 (1.6592)	4.346 (1.2240)	4.129 (1.6604)
Neutrophils; Day 29; n= 16, 18, 17, 17, 15	4.123 (1.2229)	4.591 (1.9586)	3.522 (1.4546)	3.978 (1.7026)	4.224 (2.2017)
Neutrophils; Day 43; n= 16, 20, 19, 19, 19	4.687 (1.8919)	5.049 (2.3848)	3.545 (1.4027)	4.477 (2.2480)	4.343 (1.6235)
Basophils; Day 1; n= 18, 19, 19, 20, 21	0.018 (0.0131)	0.016 (0.0134)	0.025 (0.0174)	0.028 (0.0204)	0.017 (0.0142)
Basophils; Day 15; n= 17, 19, 17, 21, 21	0.027 (0.0214)	0.026 (0.0161)	0.022 (0.0139)	0.025 (0.0325)	0.024 (0.0140)
Basophils; Day 29; n= 16, 18, 17, 17, 15	0.035 (0.0462)	0.021 (0.0128)	0.021 (0.0150)	0.024 (0.0111)	0.027 (0.0315)
Basophils; Day 43; n= 16, 20, 19, 19, 19	0.028 (0.0217)	0.018 (0.0136)	0.020 (0.0183)	0.025 (0.0204)	0.024 (0.0130)
Eosinophils; Day 1; n= 18, 19, 19, 20, 21	0.189 (0.1946)	0.174 (0.1593)	0.184 (0.1696)	0.196 (0.2310)	0.240 (0.2115)
Eosinophils; Day 15; n= 17, 19, 17, 21, 21	0.161 (0.1245)	0.166 (0.1804)	0.192 (0.2355)	0.187 (0.2186)	0.186 (0.1914)
Eosinophils; Day 29; n= 16, 18, 17, 17, 15	0.176 (0.1917)	0.149 (0.0950)	0.145 (0.1136)	0.237 (0.2785)	0.185 (0.0798)
Eosinophils; Day 43; n= 16, 20, 19, 19, 19	0.216 (0.2458)	0.210 (0.1969)	0.232 (0.2727)	0.243 (0.2670)	0.217 (0.1899)
Lymphocytes; Day 1; n= 18, 19, 19, 20, 21	1.631 (0.4264)	1.393 (0.4587)	1.739 (0.6964)	1.747 (0.7325)	1.442 (0.4998)
Lymphocytes; Day 15; n= 17, 19, 17, 21, 21	1.735 (0.6699)	1.416 (0.5670)	1.842 (0.7381)	1.526 (0.6697)	1.206 (0.4609)
Lymphocytes; Day 29; n= 16, 18, 17, 17, 15	1.870 (0.7427)	1.427 (0.4187)	1.775 (0.6767)	1.612 (0.5775)	1.181 (0.3418)
Lymphocytes; Day 43; n= 16, 20, 19, 19, 19	1.648 (0.5294)	1.509 (0.4386)	1.736 (0.3916)	1.721 (0.6644)	1.399 (0.5562)
Monocytes; Day 1; n= 18, 19, 20, 20, 21	0.401 (0.1511)	0.396 (0.1591)	0.435 (0.2703)	0.518 (0.2077)	0.421 (0.1722)
Monocytes; Day 15; n= 17, 19, 17, 21, 21	0.420 (0.2243)	0.352 (0.1457)	0.436 (0.2402)	0.446 (0.2085)	0.384 (0.2160)
Monocytes; Day 29; n= 16, 18, 17, 17, 15	0.444 (0.2076)	0.457 (0.1503)	0.403 (0.1385)	0.600 (0.3465)	0.426 (0.2628)
Monocytes; Day 43; n= 16, 20, 19, 19, 19	0.461 (0.1878)	0.459 (0.1916)	0.461 (0.2614)	0.513 (0.2739)	0.429 (0.2047)
Platelet; Day 1; n= 16, 19, 20, 19, 21	219.0 (65.04)	189.9 (36.70)	198.0 (71.03)	196.0 (61.12)	192.3 (70.85)
Platelet; Day 15; n= 17, 18, 17, 20, 21	205.4 (63.00)	175.4 (44.08)	198.5 (73.65)	194.8 (49.08)	181.5 (66.59)
Platelet; Day 29; n= 16, 19, 17, 17, 17	198.1 (76.39)	174.7 (52.50)	187.5 (62.66)	198.9 (55.07)	194.8 (81.57)
Platelet; Day 43; n= 15, 20, 19, 21, 20	220.8 (61.57)	195.8 (68.33)	188.6 (69.28)	194.1 (50.35)	170.0 (44.61)

23. Secondary Outcome

Title	Mean Corpuscular Hemoglobin (MCH) Levels in Blood at Indicated Time Points
Description	Serum MCH levels were assessed as a clinical hematology laboratory parameter from Baseline up to follow up visit at Day 43. Day 1 values were considered as Baseline values. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).
Time Frame	Up to Day 43

Outcome Measure Data

Analysis Population Description
Safety Population. One participant who was randomized to the placebo group, erroneously received 25mg daprodustat treatment throughout the 29-day treatment period. This subject is counted within the daprodustat 25mg treatment group for all PK population and safety population analyses.

Arm/Group Title	Placebo	Dapro 10 mg	Dapro 15 mg	Dapro 25 mg	Dapro 30 mg
Arm/Group Description	Randomized participants received placebo tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 10 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 15 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 25 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 30 mg tablet via oral route three times weekly for 29 days
Measure Participants	19	20	20	22	22
Day 1; n= 18, 19, 20, 20, 21	31.19 (2.538)	30.95 (1.889)	30.19 (2.145)	30.70 (1.781)	31.46 (1.942)
Day 15; n= 17, 19, 17, 21, 21	30.83 (2.100)	2.100 (1.866)	30.74 (1.476)	30.85 (1.619)	31.70 (2.315)
Day 29; n= 16, 19, 17, 18, 17	30.97 (2.290)	31.60 (2.194)	30.56 (2.236)	31.16 (1.729)	31.68 (2.224)
Day 43; n= 16, 20, 19, 21, 20	30.86 (1.992)	31.04 (1.870)	30.49 (2.155)	30.67 (1.846)	31.84 (2.143)

24. Secondary Outcome

Title	Mean Corpuscular Hemoglobin Concentration (MCHC) Levels in Blood at Indicated Time Points
Description	Serum MCHC levels were assessed as a clinical hematology laboratory parameter from Baseline up to follow up visit at Day 43. Day 1 values were considered as Baseline values. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).
Time Frame	Up to Day 43

Outcome Measure Data

Analysis Population Description
Safety Population. One participant who was randomized to the placebo group, erroneously received 25mg daprodustat treatment throughout the 29-day treatment period. This subject is counted within the daprodustat 25mg treatment group for all PK population and safety population analyses.

Arm/Group Title	Placebo	Dapro 10 mg	Dapro 15 mg	Dapro 25 mg	Dapro 30 mg
Arm/Group Description	Randomized participants received placebo tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 10 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 15 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 25 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 30 mg tablet via oral route three times weekly for 29 days
Measure Participants	19	20	20	22	22
Day 1; n= 18, 19, 20, 20, 21	322.9 (13.39)	321.7 (12.61)	319.5 (15.36)	321.5 (12.91)	327.6 (12.65)
Day 15; n= 17, 19, 17, 21, 21	321.5 (11.22)	324.0 (7.79)	324.8 (8.35)	318.3 (12.06)	322.7 (14.75)
Day 29; n= 16, 19, 17, 18, 17	323.3 (14.90)	329.6 (12.61)	325.4 (10.25)	323.6 (8.61)	323.9 (11.73)
Day 43; n= 16, 20, 19, 21, 20	321.9 (13.22)	325.2 (11.98)	325.5 (11.23)	321.0 (11.00)	327.0 (10.66)

25. Secondary Outcome

Title	Mean Corpuscular Volume (MCV) Levels in Blood at Indicated Time Points
Description	Serum MCV levels were assessed as a clinical hematology laboratory parameter from Baseline up to follow up visit at Day 43. Day 1 values were considered as Baseline values. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).
Time Frame	Up to Day 43

Outcome Measure Data

Analysis Population Description
Safety Population. One participant who was randomized to the placebo group, erroneously received 25mg daprodustat treatment throughout the 29-day treatment period. This subject is counted within the daprodustat 25mg treatment group for all PK population and safety population analyses.

Arm/Group Title	Placebo	Dapro 10 mg	Dapro 15 mg	Dapro 25 mg	Dapro 30 mg
Arm/Group Description	Randomized participants received placebo tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 10 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 15 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 25 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 30 mg tablet via oral route three times weekly for 29 days
Measure Participants	19	20	20	22	22
Day 1; n= 18, 19, 20, 20, 21	96.7 (5.94)	96.4 (5.68)	94.7 (5.28)	95.7 (4.91)	96.1 (5.61)
Day 15; n= 17, 19, 17, 21, 21	95.9 (6.02)	95.8 (6.27)	94.8 (4.53)	97.0 (6.41)	98.3 (5.57)
Day 29; n= 16, 19, 17, 18, 17	95.8 (5.83)	95.9 (6.05)	94.1 (5.94)	96.3 (4.76)	97.8 (4.96)
Day 43; n= 16, 20, 19, 21, 20	96.1 (5.91)	95.4 (5.08)	93.7 (6.09)	95.6 (5.27)	97.5 (5.98)

26. Secondary Outcome

Title	Erythrocyte Distribution Width Levels in Blood at Indicated Time Points
Description	Erythrocyte distribution width levels were assessed as a clinical hematology laboratory parameter from Baseline up to follow up visit at Day 43. Day 1 values were considered as Baseline values. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).
Time Frame	Up to Day 43

Outcome Measure Data

Analysis Population Description
Safety Population. One participant who was randomized to the placebo group, erroneously received 25mg daprodustat treatment throughout the 29-day treatment period. This subject is counted within the daprodustat 25mg treatment group for all PK population and safety population analyses.

Arm/Group Title	Placebo	Dapro 10 mg	Dapro 15 mg	Dapro 25 mg	Dapro 30 mg
Arm/Group Description	Randomized participants received placebo tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 10 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 15 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 25 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 30 mg tablet via oral route three times weekly for 29 days
Measure Participants	19	20	20	22	22
Day 1; n= 18, 19, 20, 20, 21	15.13 (2.607)	16.40 (2.082)	15.41 (1.627)	15.81 (2.504)	15.68 (1.725)
Day 15; n= 17, 19, 17, 21, 21	15.05 (2.088)	15.77 (1.569)	15.26 (1.197)	16.30 (2.331)	16.74 (1.912)
Day 29; n= 16, 19, 17, 18, 17	15.15 (2.530)	15.69 (1.750)	15.36 (1.287)	15.76 (1.253)	16.23 (1.668)
Day 43; n= 16, 20, 19, 21, 20	15.53 (2.866)	15.53 (2.018)	14.95 (1.269)	15.61 (1.297)	15.48 (1.389)

27. Secondary Outcome

Title	Change From Baseline in MCH Levels
Description	Blood samples were collected from participants to evaluate clinical hematology parameters including MCH. Change from Baseline in clinical hematology parameters at Day 15, Day 29, Day 43 are presented. Day 1 values were considered as Baseline values. Change from Baseline was calculated by subtracting post-Baseline visit values minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Time Frame	Baseline and up to Day 43

Outcome Measure Data

Analysis Population Description
Safety Population. One participant who was randomized to the placebo group, erroneously received 25mg daprodustat treatment throughout the 29-day treatment period. This subject is counted within the daprodustat 25mg treatment group for all PK population and safety population analyses.

Arm/Group Title	Placebo	Dapro 10 mg	Dapro 15 mg	Dapro 25 mg	Dapro 30 mg
Arm/Group Description	Randomized participants received placebo tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 10 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 15 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 25 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 30 mg tablet via oral route three times weekly for 29 days
Measure Participants	19	20	20	22	22
Day 15; n= 17, 19, 17, 21, 21	0.16 (0.602)	0.19 (0.817)	0.27 (0.685)	0.16 (0.520)	0.25 (0.870)
Day 29; n= 16, 19, 17, 18, 17	0.16 (0.982)	0.58 (1.185)	0.42 (0.824)	0.41 (0.744)	0.15 (0.987)
Day 43; n= 16, 20, 19, 21, 20	0.11 (0.981)	0.13 (0.948)	0.34 (0.993)	0.11 (0.842)	0.29 (0.809)

28. Secondary Outcome

Title	Change From Baseline in MCHC Levels
Description	Blood samples were collected from participants to evaluate clinical hematology parameters including MCHC. Change from Baseline in clinical hematology parameters at Day 15, Day 29, Day 43 are presented. Day 1 values were considered as Baseline values. Change from Baseline was calculated by subtracting post-Baseline visit values minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Time Frame	Baseline and up to Day 43

Outcome Measure Data

Analysis Population Description
Safety Population. One participant who was randomized to the placebo group, erroneously received 25mg daprodustat treatment throughout the 29-day treatment period. This subject is counted within the daprodustat 25mg treatment group for all PK population and safety population analyses.

Arm/Group Title	Placebo	Dapro 10 mg	Dapro 15 mg	Dapro 25 mg	Dapro 30 mg
Arm/Group Description	Randomized participants received placebo tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 10 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 15 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 25 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 30 mg tablet via oral route three times weekly for 29 days
Measure Participants	19	20	20	22	22
Day 15; n= 17, 19, 17, 21, 21	2.6 (11.09)	3.0 (14.21)	3.5 (10.87)	-3.2 (11.48)	-5.0 (12.92)
Day 29; n= 16, 19, 17, 18, 17	5.6 (12.81)	7.3 (16.92)	7.6 (8.27)	0.8 (10.04)	-4.4 (12.30)
Day 43; n= 16, 20, 19, 21, 20	3.9 (15.92)	3.0 (16.53)	6.0 (11.44)	-1.0 (12.12)	-0.3 (9.14)

29. Secondary Outcome

Title	Change From Baseline in MCV Levels
Description	Blood samples were collected from participants to evaluate clinical hematology parameters including MCV. Change from Baseline in clinical hematology parameters at Day 15, Day 29, Day 43 are presented. Day 1 values were considered as Baseline values. Change from Baseline was calculated by subtracting post-Baseline visit values minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Time Frame	Baseline and up to Day 43

Outcome Measure Data

Analysis Population Description
Safety Population. One participant who was randomized to the placebo group, erroneously received 25mg daprodustat treatment throughout the 29-day treatment period. This subject is counted within the daprodustat 25mg treatment group for all PK population and safety population analyses.

Arm/Group Title	Placebo	Dapro 10 mg	Dapro 15 mg	Dapro 25 mg	Dapro 30 mg
Arm/Group Description	Randomized participants received placebo tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 10 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 15 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 25 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 30 mg tablet via oral route three times weekly for 29 days
Measure Participants	19	20	20	22	22
Day 15; n= 17, 19, 17, 21, 21	-0.4 (2.98)	-0.2 (3.39)	-0.3 (2.57)	1.3 (3.15)	2.2 (3.21)
Day 29; n= 16, 19, 17, 18, 17	-1.4 (3.24)	-0.5 (2.86)	-0.9 (2.36)	0.9 (2.54)	1.6 (2.40)
Day 43; n= 16, 20, 19, 21, 20	-0.8 (3.15)	-0.7 (3.37)	-0.8 (3.28)	0.6 (3.06)	0.9 (2.10)

30. Secondary Outcome

Title	Change From Baseline in Erythrocyte Distribution Width Levels
Description	Blood samples were collected from participants to evaluate clinical hematology parameters including erythrocyte distribution width. Change from Baseline in clinical hematology parameters at Day 15, Day 29, Day 43 are presented. Day 1 values were considered as Baseline values. Change from Baseline was calculated by subtracting post-Baseline visit values minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Time Frame	Baseline and up to Day 43

Outcome Measure Data

Analysis Population Description
Safety Population. One participant who was randomized to the placebo group, erroneously received 25mg daprodustat treatment throughout the 29-day treatment period. This subject is counted within the daprodustat 25mg treatment group for all PK population and safety population analyses.

Arm/Group Title	Placebo	Dapro 10 mg	Dapro 15 mg	Dapro 25 mg	Dapro 30 mg
Arm/Group Description	Randomized participants received placebo tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 10 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 15 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 25 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 30 mg tablet via oral route three times weekly for 29 days
Measure Participants	19	20	20	22	22
Day 15; n= 17, 19, 17, 21, 21	-0.18 (1.025)	-0.48 (1.276)	-0.09 (1.047)	0.54 (1.162)	1.06 (1.337)
Day 29; n= 16, 19, 17, 18, 17	-0.31 (1.019)	-0.64 (1.332)	-0.23 (1.021)	0.58 (1.202)	0.40 (1.342)
Day 43; n= 16, 20, 19, 21, 20	0.18 (1.329)	-0.74 (1.728)	-0.50 (1.094)	0.23 (1.410)	-0.22 (1.165)

31. Secondary Outcome

Title	Change From Baseline in Leukocytes, Neutrophils, Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets Levels
Description	Blood samples were collected from participants to evaluate clinical hematology parameters including leukocytes, neutrophils, basophils, eosinophils, lymphocytes, monocytes, platelets. Change from Baseline in clinical hematology parameters at Day 15, Day 29, Day 43 are presented. Day 1 values were considered as Baseline values. Change from Baseline was calculated by subtracting post-Baseline visit values minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Time Frame	Baseline and up to Day 43

Outcome Measure Data

Analysis Population Description
Safety Population. One participant who was randomized to the placebo group, erroneously received 25mg daprodustat treatment throughout the 29-day treatment period. This subject is counted within the daprodustat 25mg treatment group for all PK population and safety population analyses.

Arm/Group Title	Placebo	Dapro 10 mg	Dapro 15 mg	Dapro 25 mg	Dapro 30 mg
Arm/Group Description	Randomized participants received placebo tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 10 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 15 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 25 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 30 mg tablet via oral route three times weekly for 29 days
Measure Participants	19	20	20	22	22
Leukocytes; Day 15; n= 17, 19, 17, 21, 21	0.47 (1.271)	-0.21 (1.051)	0.40 (1.116)	-0.03 (1.476)	-0.03 (1.463)
Leukocytes; Day 29; n= 16, 19, 17, 18, 17	0.49 (1.849)	0.40 (1.784)	0.00 (1.084)	-0.14 (1.701)	0.20 (1.526)
Leukocytes; Day 43; n= 16, 20, 19, 20, 19	0.54 (1.041)	1.08 (1.662)	0.23 (1.101)	0.21 (2.615)	0.67 (1.580)
Neutrophils; Day 15; n= 17, 19, 17, 21, 21	0.391 (1.2323)	-0.146 (0.9163)	0.280 (1.0681)	0.259 (1.3874)	0.344 (1.2469)
Neutrophils; Day 29; n= 16, 18, 17, 17, 15	0.237 (1.6283)	0.469 (1.5717)	-0.021 (1.0157)	-0.009 (1.8718)	0.273 (1.5729)
Neutrophils; Day 43; n= 16, 20, 19, 19, 19	0.423 (1.0535)	0.904 (1.3737)	0.112 (1.0449)	0.504 (2.3110)	0.691 (1.5221)
Basophils; Day 15; n= 17, 19, 17, 21, 21	0.005 (0.0302)	0.009 (0.0200)	-0.002 (0.0210)	-0.002 (0.0383)	0.007 (0.0102)
Basophils; Day 29; n= 16, 18, 17, 17, 15	0.013 (0.0510)	0.006 (0.0195)	-0.004 (0.0187)	0.000 (0.0242)	0.012 (0.0328)
Basophils; Day 43; n= 16, 20, 19, 19, 19	0.006 (0.0268)	0.001 (0.0148)	-0.004 (0.0203)	-0.001 (0.0228)	0.007 (0.0192)
Eosinophils; Day 15; n= 17, 19, 17, 21, 21	0.009 (0.0698)	-0.017 (0.1313)	-0.006 (0.1345)	-0.006 (0.1183)	-0.053 (0.1478)
Eosinophils; Day 29; n= 16, 18, 17, 17, 15	0.020 (0.0859)	-0.002 (0.1226)	-0.006 (0.1129)	0.025 (0.0990)	0.007 (0.0880)
Eosinophils; Day 43; n= 16, 20, 19, 19, 19	0.061 (0.1193)	0.030 (0.1439)	0.051 (0.1647)	0.021 (0.0984)	-0.024 (0.1876)
Lymphocytes; Day 15; n= 17, 19, 17, 21, 21	0.082 (0.4256)	-0.019 (0.3163)	0.106 (0.4617)	-0.208 (0.5095)	-0.236 (0.4298)
Lymphocytes; Day 29; n= 16, 18, 17, 17, 15	0.194 (0.6605)	0.026 (0.4130)	0.019 (0.4421)	-0.074 (0.7018)	-0.154 (0.3058)
Lymphocytes; Day 43; n= 16, 20, 19, 19, 19	0.018 (0.3427)	0.061 (0.3332)	0.007 (0.4824)	-0.064 (0.4759)	-0.041 (0.2801)
Monocytes; Day 15; n= 17, 19, 17, 21, 21	-0.005 (0.1518)	-0.042 (0.1504)	-0.016 (0.2285)	-0.068 (0.1895)	-0.037 (0.1460)
Monocytes; Day 29; n= 16, 18, 17, 17, 15	0.027 (0.1553)	0.053 (0.1483)	-0.031 (0.2194)	0.077 (0.2532)	0.015 (0.1878)
Monocytes; Day 43; n= 16, 20, 19, 19, 19	0.033 (0.1631)	0.065 (0.1629)	0.026 (0.2652)	-0.021 (0.1855)	0.023 (0.1249)
Platelet; Day 15; n= 17, 18, 17, 20, 21	-14.2 (26.24)	-16.2 (27.46)	-3.2 (38.13)	-3.3 (27.78)	-10.8 (31.95)
Platelet; Day 29; n= 16, 18, 17, 17, 17	-17.1 (40.58)	-12.8 (36.55)	-18.1 (29.63)	1.3 (35.58)	-2.4 (33.65)
Platelet; Day 43; n= 15, 19, 19, 21, 20	-4.9 (37.30)	4.4 (50.34)	-10.4 (35.12)	-1.6 (30.95)	-7.1 (31.95)

32. Secondary Outcome

Title	Number of Participants With Abnormal Electrocardiogram (ECG) Findings at Indicated Time Points
Description	Single measurements of 12-lead ECG were obtained in supine position using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT interval. Number of participants who had abnormal non clinically significant (NCS) and abnormal clinically significant (CS) ECG findings at Baseline (Week -4) and Day 29 are presented.
Time Frame	Up to Day 29

Outcome Measure Data

Analysis Population Description
Safety Population. One participant who was randomized to the placebo group, erroneously received 25mg daprodustat treatment throughout the 29-day treatment period. This subject is counted within the daprodustat 25mg treatment group for all PK population and safety population analyses.

Arm/Group Title	Placebo	Dapro 10 mg	Dapro 15 mg	Dapro 25 mg	Dapro 30 mg
Arm/Group Description	Randomized participants received placebo tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 10 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 15 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 25 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 30 mg tablet via oral route three times weekly for 29 days
Measure Participants	19	20	20	22	22
Baseline(Week -4);Abnormal; NCS;n=19,20,20,22,22	10 50%	15 75%	18 90%	12 57.1%	16 72.7%
Baseline(Week-4);Abnormal;CS;n=19,20,20,22,22	0 0%	0 0%	0 0%	1 4.8%	0 0%
Day 29; Abnormal; NCS; n=17,19,18,19,17	12 60%	14 70%	16 80%	8 38.1%	12 54.5%
Day 29; Abnormal; CS; n=17,19,18,19,17	0 0%	0 0%	0 0%	1 4.8%	0 0%

33. Secondary Outcome

Title	Change From Baseline in ECG Mean Heart Rate
Description	Single measurements of 12-lead ECG were obtained in supine position using an ECG machine to measure HR. Week -4 values were considered as Baseline values. Change from Baseline was calculated by subtracting post-Baseline visit values at Day 29 minus Baseline value.
Time Frame	Baseline and Day 29

Outcome Measure Data

Analysis Population Description
Safety Population

Arm/Group Title	Placebo	Dapro 10 mg	Dapro 15 mg	Dapro 25 mg	Dapro 30 mg
Arm/Group Description	Randomized participants received placebo tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 10 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 15 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 25 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 30 mg tablet via oral route three times weekly for 29 days
Measure Participants	17	19	18	19	17
Mean (Standard Deviation) [Beats per minute]	-2.0 (8.66)	0.5 (10.53)	1.1 (7.40)	2.2 (7.51)	0.9 (7.09)

34. Secondary Outcome

Title	Change From Baseline in ECG Parameters Including PR Interval, QRS Duration, QT Interval and QTcB
Description	Single measurements of 12-lead ECG were obtained in supine position using an ECG machine to measure PR interval, QRS duration, QT interval and QTcB. Week -4 values were considered as Baseline values. Change from Baseline was calculated by subtracting post-Baseline visit values at Day 29 minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Time Frame	Baseline and Day 29

Outcome Measure Data

Analysis Population Description
Safety Population. One participant who was randomized to the placebo group, erroneously received 25mg daprodustat treatment throughout the 29-day treatment period. This subject is counted within the daprodustat 25mg treatment group for all PK population and safety population analyses.

Arm/Group Title	Placebo	Dapro 10 mg	Dapro 15 mg	Dapro 25 mg	Dapro 30 mg
Arm/Group Description	Randomized participants received placebo tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 10 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 15 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 25 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 30 mg tablet via oral route three times weekly for 29 days
Measure Participants	19	20	20	22	22
PR interval; n= 17, 18, 18, 17, 16	7.8 (16.86)	7.3 (12.37)	-3.3 (23.04)	2.1 (27.13)	-11.5 (24.77)
QRS duration; n= 17, 19, 18, 19, 17	-1.4 (14.05)	-5.7 (13.36)	-4.7 (47.01)	1.7 (14.33)	2.5 (8.97)
QT interval; n= 17, 19, 18, 19, 17	10.5 (27.16)	0.7 (31.11)	-19.2 (62.37)	-1.4 (17.72)	-8.2 (33.24)
QTcB; n= 17, 19, 18, 19, 17	0.0 (30.84)	5.6 (17.40)	-3.7 (44.86)	1.1 (20.84)	-5.7 (31.65)

35. Secondary Outcome

Title	Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Pre-dialysis and Post-dialysis
Description	Vital sign measurements including SBP and DBP were taken in a seated or semi-supine position in the dialysis chair at specific time points. SBP and DBP were measured pre-dialysis and post-dialysis. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Time Frame	Up to Day 43

Outcome Measure Data

Analysis Population Description
Safety Population. One participant who was randomized to the placebo group, erroneously received 25mg daprodustat treatment throughout the 29-day treatment period. This subject is counted within the daprodustat 25mg treatment group for all PK population and safety population analyses.

Arm/Group Title	Placebo	Dapro 10 mg	Dapro 15 mg	Dapro 25 mg	Dapro 30 mg
Arm/Group Description	Randomized participants received placebo tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 10 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 15 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 25 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 30 mg tablet via oral route three times weekly for 29 days
Measure Participants	19	20	20	22	22
SBP; pre-dialysis; Day 1; n= 19, 20, 20, 22, 22	142.5 (22.15)	136.6 (15.39)	149.2 (26.36)	144.1 (24.27)	144.1 (17.01)
SBP; pre-dialysis; Day 15; n= 17, 20, 18, 22, 21	138.8 (24.12)	138.3 (16.14)	139.0 (22.77)	146.6 (20.75)	142.3 (14.90)
SBP; pre-dialysis; Day 29; n= 17, 19, 18, 19, 17	143.0 (22.08)	133.1 (18.65)	143.1 (23.21)	144.2 (23.27)	148.7 (19.17)
SBP; pre-dialysis; Day 43; n= 16, 20, 19, 21, 21	140.0 (22.01)	137.9 (13.21)	142.0 (24.23)	149.0 (23.32)	147.1 (19.18)
DBP; pre-dialysis; Day 1; n= 19, 20, 20, 22, 22	71.9 (14.84)	68.8 (11.02)	73.3 (12.96)	71.8 (14.38)	72.2 (13.64)
DBP; pre-dialysis; Day 15; n= 17, 20, 18, 22, 21	72.5 (17.76)	70.0 (11.92)	70.1 (10.50)	73.5 (13.69)	69.7 (12.43)
DBP; pre-dialysis; Day 29; n= 17, 19, 18, 19, 17	70.4 (15.43)	63.5 (13.55)	70.9 (12.86)	73.3 (13.17)	72.7 (9.96)
DBP; pre-dialysis; Day 43; n= 16, 20, 19, 21, 21	72.5 (14.73)	66.8 (11.94)	69.9 (13.54)	77.9 (16.03)	72.8 (10.52)
SBP; post-dialysis; Day 1; n= 19, 20, 20, 22, 22	138.6 (18.57)	137.0 (22.10)	139.9 (22.24)	136.7 (21.15)	140.1 (20.10)
SBP; post-dialysis; Day 15; n= 17, 20, 18, 22, 21	138.6 (21.83)	135.5 (21.63)	137.7 (23.02)	137.4 (17.58)	140.9 (15.34)
SBP; post-dialysis; Day 29; n= 17, 19, 18, 19, 17	135.7 (26.04)	130.1 (18.50)	133.7 (23.88)	142.8 (23.96)	147.8 (19.09)
SBP; post-dialysis; Day 43; n= 16, 20, 19, 21, 21	137.5 (22.74)	135.8 (21.05)	130.4 (15.47)	145.2 (20.66)	137.5 (22.74)
DBP; post-dialysis; Day 1; n= 19, 20, 20, 22, 22	72.1 (15.11)	67.9 (11.49)	68.7 (11.64)	71.1 (12.92)	71.5 (11.17)
DBP; post-dialysis; Day 15; n= 17, 20, 18, 22, 21	72.4 (16.41)	70.1 (12.84)	67.8 (11.10)	71.3 (11.07)	71.1 (9.51)
DBP; post-dialysis; Day 29; n= 17, 19, 18, 19, 17	73.9 (15.11)	64.4 (9.83)	67.9 (12.00)	72.4 (12.43)	72.9 (11.18)
DBP; post-dialysis; Day 43; n= 16, 20, 19, 21, 21	69.5 (15.24)	67.4 (10.90)	67.4 (11.24)	72.9 (12.60)	75.3 (7.89)

36. Secondary Outcome

Title	Pulse Rate Values at Pre-dialysis and Post-dialysis
Description	Vital sign measurements including pulse rate values were taken in a seated or semi-supine position in the dialysis chair. Pulse rate was measured pre-dialysis and post-dialysis. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Time Frame	Up to Day 43

Outcome Measure Data

Analysis Population Description
Safety Population. One participant who was randomized to the placebo group, erroneously received 25mg daprodustat treatment throughout the 29-day treatment period. This subject is counted within the daprodustat 25mg treatment group for all PK population and safety population analyses.

Arm/Group Title	Placebo	Dapro 10 mg	Dapro 15 mg	Dapro 25 mg	Dapro 30 mg
Arm/Group Description	Randomized participants received placebo tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 10 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 15 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 25 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 30 mg tablet via oral route three times weekly for 29 days
Measure Participants	19	20	20	22	22
Pre-dialysis; Day 1; n= 19, 20, 20, 22, 22	68.5 (7.95)	69.9 (9.18)	66.7 (7.01)	71.4 (11.25)	76.5 (9.35)
Pre-dialysis; Day 15; n= 17, 20, 18, 22, 21	76.1 (10.31)	67.3 (9.20)	68.3 (7.51)	72.1 (11.89)	75.1 (12.68)
Pre-dialysis; Day 29; n= 17, 19, 18, 19, 17	70.4 (8.31)	70.3 (11.54)	69.6 (9.53)	70.8 (9.91)	73.4 (11.45)
Pre-dialysis; Day 43; n= 16, 20, 19, 21, 21	71.5 (9.17)	69.9 (9.34)	66.9 (6.74)	71.3 (10.08)	75.8 (8.29)
Post-dialysis; Day 1; n= 19, 20, 20, 22, 22	71.0 (11.54)	68.7 (11.19)	66.3 (8.37)	73.2 (12.77)	78.8 (11.61)
Post-dialysis; Day 15; n= 17, 20, 18, 22, 21	72.5 (12.69)	67.7 (12.24)	70.1 (12.49)	73.0 (12.07)	78.1 (15.72)
Post-dialysis; Day 29; n= 17, 19, 18, 19, 17	73.6 (7.10)	69.9 (9.60)	68.8 (11.29)	72.2 (9.52)	77.4 (10.04)
Post-dialysis; Day 43; n= 16, 20, 19, 21, 21	72.0 (12.04)	69.1 (10.21)	68.0 (10.28)	71.9 (11.02)	77.3 (10.26)

37. Secondary Outcome

Title	Weight Values at Post-dialysis
Description	Vital sign measurements including weight values were taken in a seated or semi-supine position in the dialysis chair. Weight was measured post-dialysis. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Time Frame	Up to Day 43

Outcome Measure Data

Analysis Population Description
Safety Population. One participant who was randomized to the placebo group, erroneously received 25mg daprodustat treatment throughout the 29-day treatment period. This subject is counted within the daprodustat 25mg treatment group for all PK population and safety population analyses.

Arm/Group Title	Placebo	Dapro 10 mg	Dapro 15 mg	Dapro 25 mg	Dapro 30 mg
Arm/Group Description	Randomized participants received placebo tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 10 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 15 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 25 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 30 mg tablet via oral route three times weekly for 29 days
Measure Participants	19	20	20	22	22
Day 1; n= 19, 20, 20, 22, 22	82.38 (25.941)	80.04 (25.996)	78.83 (21.331)	79.38 (23.345)	76.03 (16.877)
Day 15; n= 17, 20, 18, 22, 21	84.24 (26.652)	80.00 (25.887)	79.82 (22.200)	79.44 (23.500)	75.55 (17.595)
Day 29; n= 17, 19, 18, 19, 17	83.22 (27.198)	81.04 (25.925)	80.02 (22.286)	82.66 (23.036)	76.07 (18.135)
Day 43; n= 16, 20, 19, 21, 21	83.93 (27.589)	80.21 (26.683)	79.25 (21.757)	80.64 (23.347)	73.66 (11.614)

38. Secondary Outcome

Title	Change From Baseline in SBP and DBP Values at Pre-dialysis and Post-dialysis
Description	Vital sign measurements including SBP and DBP were taken in a seated or semi-supine position in the dialysis chair. SBP and DBP were measured pre-dialysis and post-dialysis. Pre-dialysis Baseline value was defined as SBP and DBP value obtained pre-dialysis on Day 1. Post-dialysis Baseline value was defined as SBP and DBP value obtained post-dialysis at Week -2. Change from Baseline was calculated by subtracting post-Baseline visit values minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Time Frame	Up to Day 43

Outcome Measure Data

Analysis Population Description
Safety Population. One participant who was randomized to the placebo group, erroneously received 25mg daprodustat treatment throughout the 29-day treatment period. This subject is counted within the daprodustat 25mg treatment group for all PK population and safety population analyses.

Arm/Group Title	Placebo	Dapro 10 mg	Dapro 15 mg	Dapro 25 mg	Dapro 30 mg
Arm/Group Description	Randomized participants received placebo tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 10 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 15 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 25 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 30 mg tablet via oral route three times weekly for 29 days
Measure Participants	19	20	20	22	22
SBP; pre-dialysis; Day 15; n= 17, 20, 18, 22, 21	-2.9 (22.03)	1.7 (14.14)	-5.6 (14.77)	2.5 (20.68)	-1.4 (16.35)
SBP; pre-dialysis; Day 29; n= 17, 19, 18, 19, 17	-0.6 (20.32)	-3.9 (19.72)	-4.7 (18.17)	1.3 (17.51)	4.5 (20.03)
SBP; pre-dialysis; Day 43; n= 16, 20, 19, 21, 21	-2.1 (21.34)	1.2 (17.14)	-6.2 (13.83)	3.3 (19.47)	4.3 (10.03)
SBP; post-dialysis; Day 15; n= 17, 20, 18, 22, 21	5.4 (21.39)	-3.6 (20.13)	6.1 (20.81)	5.7 (21.07)	-0.7 (22.33)
SBP; post-dialysis; Day 29; n= 17, 19, 18, 19, 17	2.3 (19.72)	-9.4 (18.50)	0.8 (24.79)	9.3 (19.03)	4.0 (19.76)
SBP; post-dialysis; Day 43; n= 16, 20, 19, 21, 21	3.1 (22.22)	-3.2 (21.71)	-3.6 (17.88)	12.0 (20.19)	4.7 (20.11)
DBP; pre-dialysis; Day 15; n= 17, 20, 18, 22, 21	1.1 (10.57)	1.2 (8.85)	-1.7 (9.78)	1.8 (12.68)	-2.1 (11.04)
DBP; pre-dialysis; Day 29; n= 17, 19, 18, 19, 17	-0.3 (11.09)	-4.7 (10.04)	-3.0 (8.99)	1.4 (10.50)	-0.1 (13.80)
DBP; pre-dialysis; Day 43; n= 16, 20, 19, 21, 21	2.2 (8.80)	-2.0 (9.47)	-3.1 (11.06)	5.2 (15.08)	2.1 (11.00)
DBP; post-dialysis; Day 15; n= 17, 20, 18, 22, 21	2.4 (11.41)	2.4 (7.71)	-2.9 (11.11)	3.6 (9.84)	-0.8 (14.13)
DBP; post-dialysis; Day 29; n= 17, 19, 18, 19, 17	3.7 (12.93)	-2.5 (8.52)	-3.2 (11.61)	4.1 (9.33)	0.2 (10.59)
DBP; post-dialysis; Day 43; n= 16, 20, 19, 21, 21	-0.6 (10.07)	-0.3 (9.53)	-3.8 (12.13)	4.5 (9.99)	4.8 (10.28)

39. Secondary Outcome

Title	Change From Baseline in Pulse Rate Value at Pre-dialysis and Post-dialysis
Description	Vital sign measurements including pulse rate were taken in a seated or semi-supine position in the dialysis chair. Pulse rate was measured pre-dialysis and post-dialysis. Pre-dialysis Baseline value was defined as pulse rate value obtained pre-dialysis on Day 1. Post-dialysis Baseline value was defined as pulse rate value obtained post-dialysis at Week -2. Change from Baseline was calculated by subtracting post-Baseline visit values minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Time Frame	Up to Day 43

Outcome Measure Data

Analysis Population Description
Safety Population. One participant who was randomized to the placebo group, erroneously received 25mg daprodustat treatment throughout the 29-day treatment period. This subject is counted within the daprodustat 25mg treatment group for all PK population and safety population analyses.

Arm/Group Title	Placebo	Dapro 10 mg	Dapro 15 mg	Dapro 25 mg	Dapro 30 mg
Arm/Group Description	Randomized participants received placebo tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 10 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 15 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 25 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 30 mg tablet via oral route three times weekly for 29 days
Measure Participants	19	20	20	22	22
Pre-dialysis; Day 15; n= 17, 20, 18, 22, 21	7.0 (9.50)	-2.6 (8.46)	2.3 (5.76)	0.7 (11.46)	-1.4 (11.15)
Pre-dialysis; Day 29; n= 17, 19, 18, 19, 17	2.4 (6.92)	0.9 (12.86)	3.4 (7.58)	0.5 (10.01)	-3.0 (9.14)
Pre-dialysis; Day 43; n= 16, 20, 19, 21, 21	3.1 (9.59)	0.1 (6.57)	0.8 (6.11)	-0.6 (10.03)	0.2 (6.79)
Post-dialysis; Day 15; n= 17, 20, 18, 22, 21	2.2 (11.61)	-1.2 (12.86)	1.1 (10.15)	0.5 (8.00)	4.4 (13.28)
Post-dialysis; Day 29; n= 17, 19, 18, 19, 17	4.2 (9.13)	1.5 (13.13)	-0.8 (9.79)	2.6 (9.04)	6.0 (7.50)
Post-dialysis; Day 43; n= 16, 20, 19, 21, 21	2.3 (8.67)	0.3 (12.96)	-0.8 (9.32)	-0.1 (9.08)	3.9 (9.32)

40. Secondary Outcome

Title	Change From Baseline in Weight at Post-dialysis
Description	Vital sign measurements including weight were taken in a seated or semi-supine position in the dialysis chair. Weight was measured post-dialysis. Post-dialysis Baseline value was defined as SBP and DBP value obtained post-dialysis at Week -2. Change from Baseline was calculated by subtracting post-Baseline visit values minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Time Frame	Up to Day 43

Outcome Measure Data

Analysis Population Description
Safety Population. One participant who was randomized to the placebo group, erroneously received 25mg daprodustat treatment throughout the 29-day treatment period. This subject is counted within the daprodustat 25mg treatment group for all PK population and safety population analyses.

Arm/Group Title	Placebo	Dapro 10 mg	Dapro 15 mg	Dapro 25 mg	Dapro 30 mg
Arm/Group Description	Randomized participants received placebo tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 10 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 15 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 25 mg tablet via oral route three times weekly for 29 days.	Randomized participants received dapro 30 mg tablet via oral route three times weekly for 29 days
Measure Participants	19	20	20	22	22
Day 15; n= 17, 20, 18, 22, 21	-0.16 (0.634)	0.16 (0.971)	-0.01 (0.617)	0.06 (0.799)	-0.31 (1.215)
Day 29; n= 17, 19, 18, 19, 17	-0.11 (1.053)	-0.05 (1.583)	-1.23 (5.913)	-0.16 (1.046)	-0.19 (1.244)
Day 43; n= 16, 20, 19, 21, 21	-0.21 (0.665)	0.37 (2.760)	-1.39 (5.759)	0.15 (1.472)	0.33 (2.169)

Adverse Events

	Placebo		Dapro 10 mg		Dapro 15 mg		Dapro 25 mg		Dapro 30 mg
Time Frame	On-therapy serious adverse events (SAEs) and non-serious adverse events (AEs) are presented from the start of study treatment to the end of the 29-day study treatment period plus 1 day, inclusive; an average of 30 days.
Adverse Event Reporting Description	On-therapy SAEs and non-serious AEs are reported for members of the safety Population, comprised of all participants who received at least one dose of investigational drug. One participant who was randomized to the placebo group, erroneously received 25mg daprodustat treatment throughout the 29-day treatment period. This subject is counted within the daprodustat 25mg treatment group for all PK population and safety population analyses.

Arm/Group Title	Placebo		Dapro 10 mg		Dapro 15 mg		Dapro 25 mg		Dapro 30 mg
Arm/Group Description	Randomized participants received placebo tablet via oral route three times weekly for 29 days.		Randomized participants received dapro 10 mg tablet via oral route three times weekly for 29 days.		Randomized participants received dapro 15 mg tablet via oral route three times weekly for 29 days.		Randomized participants received dapro 25 mg tablet via oral route three times weekly for 29 days.		Randomized participants received dapro 30 mg tablet via oral route three times weekly for 29 days
All Cause Mortality
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/19 (0%)		0/20 (0%)		0/20 (0%)		0/22 (0%)		0/22 (0%)
Serious Adverse Events
	Placebo		Dapro 10 mg		Dapro 15 mg		Dapro 25 mg		Dapro 30 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/19 (10.5%)		3/20 (15%)		2/20 (10%)		1/22 (4.5%)		2/22 (9.1%)
Cardiac disorders
Angina unstable	0/19 (0%)	0	1/20 (5%)	1	0/20 (0%)	0	0/22 (0%)	0	1/22 (4.5%)	1
Cardiac failure congestive	0/19 (0%)	0	2/20 (10%)	2	0/20 (0%)	0	0/22 (0%)	0	0/22 (0%)	0
Gastrointestinal disorders
Mesenteric artery stenosis	0/19 (0%)	0	0/20 (0%)	0	1/20 (5%)	1	0/22 (0%)	0	0/22 (0%)	0
Injury, poisoning and procedural complications
Arteriovenous fistula thrombosis	1/19 (5.3%)	1	0/20 (0%)	0	0/20 (0%)	0	0/22 (0%)	0	0/22 (0%)	0
Post procedural myocardial infarction	0/19 (0%)	0	1/20 (5%)	1	0/20 (0%)	0	0/22 (0%)	0	0/22 (0%)	0
Metabolism and nutrition disorders
Fluid overload	0/19 (0%)	0	0/20 (0%)	0	0/20 (0%)	0	1/22 (4.5%)	1	1/22 (4.5%)	1
Vascular disorders
Hypertensive crisis	0/19 (0%)	0	0/20 (0%)	0	1/20 (5%)	1	0/22 (0%)	0	0/22 (0%)	0
Orthostatic hypotension	1/19 (5.3%)	1	0/20 (0%)	0	0/20 (0%)	0	0/22 (0%)	0	0/22 (0%)	0
Other (Not Including Serious) Adverse Events
	Placebo		Dapro 10 mg		Dapro 15 mg		Dapro 25 mg		Dapro 30 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/19 (26.3%)		8/20 (40%)		4/20 (20%)		2/22 (9.1%)		0/22 (0%)
Cardiac disorders
Bundle branch block left	0/19 (0%)	0	0/20 (0%)	0	1/20 (5%)	1	0/22 (0%)	0	0/22 (0%)	0
Endocrine disorders
Hyperparathyroidism	0/19 (0%)	0	1/20 (5%)	1	0/20 (0%)	0	0/22 (0%)	0	0/22 (0%)	0
Gastrointestinal disorders
Diarrhoea	0/19 (0%)	0	2/20 (10%)	2	0/20 (0%)	0	0/22 (0%)	0	0/22 (0%)	0
Dyspepsia	0/19 (0%)	0	0/20 (0%)	0	1/20 (5%)	1	0/22 (0%)	0	0/22 (0%)	0
Gastrooesophageal reflux disease	0/19 (0%)	0	1/20 (5%)	1	0/20 (0%)	0	0/22 (0%)	0	0/22 (0%)	0
Vomiting	0/19 (0%)	0	1/20 (5%)	1	0/20 (0%)	0	0/22 (0%)	0	0/22 (0%)	0
General disorders
Asthenia	1/19 (5.3%)	1	0/20 (0%)	0	1/20 (5%)	1	0/22 (0%)	0	0/22 (0%)	0
Pyrexia	0/19 (0%)	0	0/20 (0%)	0	1/20 (5%)	1	0/22 (0%)	0	0/22 (0%)	0
Infections and infestations
Helicobacter gastritis	1/19 (5.3%)	1	0/20 (0%)	0	0/20 (0%)	0	0/22 (0%)	0	0/22 (0%)	0
Pneumonia	0/19 (0%)	0	1/20 (5%)	1	0/20 (0%)	0	0/22 (0%)	0	0/22 (0%)	0
Upper respiratory tract infection	0/19 (0%)	0	1/20 (5%)	1	0/20 (0%)	0	0/22 (0%)	0	0/22 (0%)	0
Viral infection	0/19 (0%)	0	1/20 (5%)	1	0/20 (0%)	0	0/22 (0%)	0	0/22 (0%)	0
Injury, poisoning and procedural complications
Arteriovenous fistula site haemorrhage	0/19 (0%)	0	1/20 (5%)	1	0/20 (0%)	0	0/22 (0%)	0	0/22 (0%)	0
Procedural hypotension	0/19 (0%)	0	1/20 (5%)	1	0/20 (0%)	0	1/22 (4.5%)	1	0/22 (0%)	0
Metabolism and nutrition disorders
Dehydration	1/19 (5.3%)	1	0/20 (0%)	0	0/20 (0%)	0	0/22 (0%)	0	0/22 (0%)	0
Hypoglycaemia	0/19 (0%)	0	1/20 (5%)	1	0/20 (0%)	0	0/22 (0%)	0	0/22 (0%)	0
Musculoskeletal and connective tissue disorders
Muscle spasms	0/19 (0%)	0	0/20 (0%)	0	1/20 (5%)	1	0/22 (0%)	0	0/22 (0%)	0
Musculoskeletal pain	1/19 (5.3%)	1	0/20 (0%)	0	0/20 (0%)	0	0/22 (0%)	0	0/22 (0%)	0
Nervous system disorders
Dizziness	1/19 (5.3%)	1	1/20 (5%)	1	0/20 (0%)	0	0/22 (0%)	0	0/22 (0%)	0
Headache	1/19 (5.3%)	1	0/20 (0%)	0	0/20 (0%)	0	0/22 (0%)	0	0/22 (0%)	0
Psychiatric disorders
Depression	0/19 (0%)	0	0/20 (0%)	0	1/20 (5%)	1	0/22 (0%)	0	0/22 (0%)	0
Respiratory, thoracic and mediastinal disorders
Catarrh	0/19 (0%)	0	1/20 (5%)	1	0/20 (0%)	0	0/22 (0%)	0	0/22 (0%)	0
Vascular disorders
Hypotension	0/19 (0%)	0	1/20 (5%)	1	1/20 (5%)	1	1/22 (4.5%)	1	0/22 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

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

Results Point of Contact

Name/Title	GSK Response Center
Organization	GlaxoSmithKline
Phone	866-435-7343
Email	GSKClinicalSupportHD@gsk.com

Responsible Party:

GlaxoSmithKline

ClinicalTrials.gov Identifier:

NCT02689206

Other Study ID Numbers:

204836
2015-004790-32

First Posted:

Feb 23, 2016

Last Update Posted:

Feb 25, 2020

Last Verified:

Feb 1, 2020

Study to Evaluate the Efficacy, Safety and Pharmacokinetics of Three-times Weekly Dosing of GSK1278863 in Hemodialysis-dependent Subjects With Anemia Associated With Chronic Kidney Disease Who Are Switched From a Stable Dose of an Erythropoiesis-stimulating Agent

Study Details

Study Description

Brief Summary

Study Design

Arms and Interventions

Outcome Measures

Primary Outcome Measures

Secondary Outcome Measures

Eligibility Criteria

Criteria

Inclusion Criteria:

Exclusion Criteria:

Contacts and Locations

Locations

Sponsors and Collaborators

Investigators

Study Documents (Full-Text)

More Information

Publications

Study Results

Participant Flow

Baseline Characteristics

Outcome Measures

Outcome Measure Data

Statistical Analysis 1

Statistical Analysis 2

Statistical Analysis 3

Statistical Analysis 4

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Adverse Events

All Cause Mortality

Serious Adverse Events

Other (Not Including Serious) Adverse Events

Limitations/Caveats

More Information

Certain Agreements

Results Point of Contact