Anaemia
Conditions
Keywords
Chronic kidney disease, Efficacy, Erythropoiesis-stimulating agent, GSK1278863, Safety, Hemodialysis-dependent anemia, Pharmacokinetics
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.
Interventions
DRUGGSK1278863
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.
DRUGGSK1278863 matching Placebo
GSK1278863 matching placebo will be supplied as a round, biconvex, 10 mm white film coated tablet.
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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). |
| 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). |
| 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. |
| 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). |
| 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). |
| 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). |
| 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). |
Countries
Canada, Germany, Russia, Spain, United States
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 details
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
Participants by arm
| Arm | Count |
|---|---|
| Placebo Randomized participants received placebo tablet via oral route three times weekly for 29 days. | 20 |
| Dapro 10 mg Randomized participants received dapro 10 mg tablet via oral route three times weekly for 29 days. | 20 |
| Dapro 15 mg Randomized participants received dapro 15 mg tablet via oral route three times weekly for 29 days. | 20 |
| Dapro 25 mg Randomized participants received dapro 25 mg tablet via oral route three times weekly for 29 days. | 21 |
| Dapro 30 mg Randomized participants received dapro 30 mg tablet via oral route three times weekly for 29 days | 22 |
| Total | 103 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 1 | 0 | 2 |
| Overall Study | Other: Reached stopping criteria | 0 | 1 | 2 | 3 | 4 |
| Overall Study | Physician Decision | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Protocol Violation | 1 | 0 | 0 | 1 | 2 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Placebo | Total | Dapro 30 mg | Dapro 25 mg | Dapro 15 mg | Dapro 10 mg |
|---|---|---|---|---|---|---|
| Age, Continuous | 61.0 Years STANDARD_DEVIATION 13.06 | 63.4 Years STANDARD_DEVIATION 14.39 | 65.4 Years STANDARD_DEVIATION 13.97 | 67.2 Years STANDARD_DEVIATION 15.22 | 59.5 Years STANDARD_DEVIATION 12.26 | 63.6 Years STANDARD_DEVIATION 16.98 |
| Race/Ethnicity, Customized Race customized African American/African Heritage | 6 Participants | 30 Participants | 6 Participants | 5 Participants | 7 Participants | 6 Participants |
| Race/Ethnicity, Customized Race customized American Indian Or Alaskan Native | 0 Participants | 2 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Race customized Asian - Central/South Asian Heritage | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Race customized Native Hawaiian Or Other Pacific Islander | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Race customized White- Arabic/North African Heritage | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Race customized White-White/Caucasian/European Heritage | 14 Participants | 67 Participants | 15 Participants | 14 Participants | 12 Participants | 12 Participants |
| Sex: Female, Male Female | 11 Participants | 42 Participants | 8 Participants | 9 Participants | 6 Participants | 8 Participants |
| Sex: Female, Male Male | 9 Participants | 61 Participants | 14 Participants | 12 Participants | 14 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 19 | 0 / 20 | 0 / 20 | 0 / 22 | 0 / 22 |
| other Total, other adverse events | 5 / 19 | 8 / 20 | 4 / 20 | 2 / 22 | 0 / 22 |
| serious Total, serious adverse events | 2 / 19 | 3 / 20 | 2 / 20 | 1 / 22 | 2 / 22 |
Outcome results
Primary
Change From Baseline in Hgb Levels at 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.
Time frame: Baseline and Day 29
Population: ITT Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Hgb Levels at Day 29 | -0.61 g/dL | Standard Deviation 0.646 |
| Dapro 10 mg | Change From Baseline in Hgb Levels at Day 29 | -0.19 g/dL | Standard Deviation 1.75 |
| Dapro 15 mg | Change From Baseline in Hgb Levels at Day 29 | -0.13 g/dL | Standard Deviation 1.088 |
| Dapro 25 mg | Change From Baseline in Hgb Levels at Day 29 | 0.64 g/dL | Standard Deviation 1.453 |
| Dapro 30 mg | Change From Baseline in Hgb Levels at Day 29 | 0.55 g/dL | Standard Deviation 1.167 |
95% CI: [-0.31, 1.45]
95% CI: [-0.4, 1.42]
95% CI: [0.59, 2.35]
95% CI: [0.77, 2.57]
Secondary
Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Alkaline Phosphatase (Alk. Phosph) Levels in Blood at Indicated Time Points
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Alkaline Phosphatase (Alk. Phosph) Levels in Blood at Indicated Time Points | Alk. phosph; Day 1; n= 18, 20, 20, 22, 22 | 97.0 IU/L | Standard Deviation 33.07 |
| Placebo | Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Alkaline Phosphatase (Alk. Phosph) Levels in Blood at Indicated Time Points | ALT; Day 29; n= 17, 19, 18, 19, 17 | 24.4 IU/L | Standard Deviation 32.34 |
| Placebo | Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Alkaline Phosphatase (Alk. Phosph) Levels in Blood at Indicated Time Points | ALT; Day 1; n= 18, 20, 20, 22, 22 | 12.6 IU/L | Standard Deviation 9.36 |
| Placebo | Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Alkaline Phosphatase (Alk. Phosph) Levels in Blood at Indicated Time Points | Alk. phosph.; Day 43; n= 15, 20, 18, 21,21 | 96.5 IU/L | Standard Deviation 34.12 |
| Placebo | Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Alkaline Phosphatase (Alk. Phosph) Levels in Blood at Indicated Time Points | ALT; Day 15; n= 17, 20, 18, 22, 20 | 16.5 IU/L | Standard Deviation 13.8 |
| Placebo | Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Alkaline Phosphatase (Alk. Phosph) Levels in Blood at Indicated Time Points | AST; Day 29; n= 17, 19, 18, 19, 17 | 26.8 IU/L | Standard Deviation 30.04 |
| Placebo | Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Alkaline Phosphatase (Alk. Phosph) Levels in Blood at Indicated Time Points | AST; Day 1; n= 18, 20, 20, 22, 22 | 14.9 IU/L | Standard Deviation 5.58 |
| Placebo | Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Alkaline Phosphatase (Alk. Phosph) Levels in Blood at Indicated Time Points | Alk. phosph.; Day 29; n= 17, 19, 18, 19,17 | 94.1 IU/L | Standard Deviation 35.07 |
| Placebo | Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Alkaline Phosphatase (Alk. Phosph) Levels in Blood at Indicated Time Points | Alk. phosph; Day 15; n= 17, 20, 18, 22,20 | 102.4 IU/L | Standard Deviation 34.7 |
| Placebo | Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Alkaline Phosphatase (Alk. Phosph) Levels in Blood at Indicated Time Points | AST; Day 43; n= 15, 20, 18, 21, 21 | 15.9 IU/L | Standard Deviation 6.65 |
| Placebo | Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Alkaline Phosphatase (Alk. Phosph) Levels in Blood at Indicated Time Points | AST; Day 15; n= 17, 20, 18, 22, 20 | 17.1 IU/L | Standard Deviation 7.3 |
| Placebo | Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Alkaline Phosphatase (Alk. Phosph) Levels in Blood at Indicated Time Points | ALT; Day 43; n= 15, 20, 18, 21, 21 | 14.3 IU/L | Standard Deviation 8.55 |
| Dapro 10 mg | Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Alkaline Phosphatase (Alk. Phosph) Levels in Blood at Indicated Time Points | ALT; Day 43; n= 15, 20, 18, 21, 21 | 13.8 IU/L | Standard Deviation 8.03 |
| Dapro 10 mg | Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Alkaline Phosphatase (Alk. Phosph) Levels in Blood at Indicated Time Points | AST; Day 1; n= 18, 20, 20, 22, 22 | 14.2 IU/L | Standard Deviation 5.19 |
| Dapro 10 mg | Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Alkaline Phosphatase (Alk. Phosph) Levels in Blood at Indicated Time Points | AST; Day 29; n= 17, 19, 18, 19, 17 | 13.8 IU/L | Standard Deviation 5.01 |
| Dapro 10 mg | Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Alkaline Phosphatase (Alk. Phosph) Levels in Blood at Indicated Time Points | Alk. phosph; Day 1; n= 18, 20, 20, 22, 22 | 112.3 IU/L | Standard Deviation 74.61 |
| Dapro 10 mg | Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Alkaline Phosphatase (Alk. Phosph) Levels in Blood at Indicated Time Points | ALT; Day 1; n= 18, 20, 20, 22, 22 | 13.4 IU/L | Standard Deviation 7.51 |
| Dapro 10 mg | Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Alkaline Phosphatase (Alk. Phosph) Levels in Blood at Indicated Time Points | ALT; Day 15; n= 17, 20, 18, 22, 20 | 13.9 IU/L | Standard Deviation 10.58 |
| Dapro 10 mg | Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Alkaline Phosphatase (Alk. Phosph) Levels in Blood at Indicated Time Points | ALT; Day 29; n= 17, 19, 18, 19, 17 | 12.8 IU/L | Standard Deviation 6.43 |
| Dapro 10 mg | Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Alkaline Phosphatase (Alk. Phosph) Levels in Blood at Indicated Time Points | AST; Day 15; n= 17, 20, 18, 22, 20 | 14.3 IU/L | Standard Deviation 5.67 |
| Dapro 10 mg | Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Alkaline Phosphatase (Alk. Phosph) Levels in Blood at Indicated Time Points | Alk. phosph; Day 15; n= 17, 20, 18, 22,20 | 115.4 IU/L | Standard Deviation 73.37 |
| Dapro 10 mg | Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Alkaline Phosphatase (Alk. Phosph) Levels in Blood at Indicated Time Points | AST; Day 43; n= 15, 20, 18, 21, 21 | 14.9 IU/L | Standard Deviation 6.07 |
| Dapro 10 mg | Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Alkaline Phosphatase (Alk. Phosph) Levels in Blood at Indicated Time Points | Alk. phosph.; Day 29; n= 17, 19, 18, 19,17 | 120.2 IU/L | Standard Deviation 81.15 |
| Dapro 10 mg | Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Alkaline Phosphatase (Alk. Phosph) Levels in Blood at Indicated Time Points | Alk. phosph.; Day 43; n= 15, 20, 18, 21,21 | 117.6 IU/L | Standard Deviation 76.61 |
| Dapro 15 mg | Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Alkaline Phosphatase (Alk. Phosph) Levels in Blood at Indicated Time Points | Alk. phosph.; Day 43; n= 15, 20, 18, 21,21 | 113.8 IU/L | Standard Deviation 78.69 |
| Dapro 15 mg | Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Alkaline Phosphatase (Alk. Phosph) Levels in Blood at Indicated Time Points | Alk. phosph.; Day 29; n= 17, 19, 18, 19,17 | 109.2 IU/L | Standard Deviation 83.14 |
| Dapro 15 mg | Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Alkaline Phosphatase (Alk. Phosph) Levels in Blood at Indicated Time Points | AST; Day 29; n= 17, 19, 18, 19, 17 | 16.0 IU/L | Standard Deviation 8.44 |
| Dapro 15 mg | Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Alkaline Phosphatase (Alk. Phosph) Levels in Blood at Indicated Time Points | ALT; Day 43; n= 15, 20, 18, 21, 21 | 12.8 IU/L | Standard Deviation 6.89 |
| Dapro 15 mg | Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Alkaline Phosphatase (Alk. Phosph) Levels in Blood at Indicated Time Points | AST; Day 43; n= 15, 20, 18, 21, 21 | 17.2 IU/L | Standard Deviation 11.4 |
| Dapro 15 mg | Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Alkaline Phosphatase (Alk. Phosph) Levels in Blood at Indicated Time Points | Alk. phosph; Day 15; n= 17, 20, 18, 22,20 | 114.5 IU/L | Standard Deviation 82.29 |
| Dapro 15 mg | Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Alkaline Phosphatase (Alk. Phosph) Levels in Blood at Indicated Time Points | Alk. phosph; Day 1; n= 18, 20, 20, 22, 22 | 106.8 IU/L | Standard Deviation 84.85 |
| Dapro 15 mg | Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Alkaline Phosphatase (Alk. Phosph) Levels in Blood at Indicated Time Points | ALT; Day 29; n= 17, 19, 18, 19, 17 | 12.2 IU/L | Standard Deviation 6.4 |
| Dapro 15 mg | Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Alkaline Phosphatase (Alk. Phosph) Levels in Blood at Indicated Time Points | ALT; Day 1; n= 18, 20, 20, 22, 22 | 14.6 IU/L | Standard Deviation 11.39 |
| Dapro 15 mg | Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Alkaline Phosphatase (Alk. Phosph) Levels in Blood at Indicated Time Points | AST; Day 1; n= 18, 20, 20, 22, 22 | 17.2 IU/L | Standard Deviation 12.31 |
| Dapro 15 mg | Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Alkaline Phosphatase (Alk. Phosph) Levels in Blood at Indicated Time Points | ALT; Day 15; n= 17, 20, 18, 22, 20 | 12.4 IU/L | Standard Deviation 7.87 |
| Dapro 15 mg | Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Alkaline Phosphatase (Alk. Phosph) Levels in Blood at Indicated Time Points | AST; Day 15; n= 17, 20, 18, 22, 20 | 15.0 IU/L | Standard Deviation 7.72 |
| Dapro 25 mg | Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Alkaline Phosphatase (Alk. Phosph) Levels in Blood at Indicated Time Points | Alk. phosph; Day 15; n= 17, 20, 18, 22,20 | 101.5 IU/L | Standard Deviation 56.44 |
| Dapro 25 mg | Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Alkaline Phosphatase (Alk. Phosph) Levels in Blood at Indicated Time Points | Alk. phosph.; Day 43; n= 15, 20, 18, 21,21 | 116.2 IU/L | Standard Deviation 96.02 |
| Dapro 25 mg | Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Alkaline Phosphatase (Alk. Phosph) Levels in Blood at Indicated Time Points | ALT; Day 29; n= 17, 19, 18, 19, 17 | 10.9 IU/L | Standard Deviation 5.67 |
| Dapro 25 mg | Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Alkaline Phosphatase (Alk. Phosph) Levels in Blood at Indicated Time Points | ALT; Day 43; n= 15, 20, 18, 21, 21 | 13.1 IU/L | Standard Deviation 5.19 |
| Dapro 25 mg | Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Alkaline Phosphatase (Alk. Phosph) Levels in Blood at Indicated Time Points | AST; Day 1; n= 18, 20, 20, 22, 22 | 14.4 IU/L | Standard Deviation 5.85 |
| Dapro 25 mg | Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Alkaline Phosphatase (Alk. Phosph) Levels in Blood at Indicated Time Points | Alk. phosph; Day 1; n= 18, 20, 20, 22, 22 | 99.4 IU/L | Standard Deviation 47.26 |
| Dapro 25 mg | Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Alkaline Phosphatase (Alk. Phosph) Levels in Blood at Indicated Time Points | AST; Day 29; n= 17, 19, 18, 19, 17 | 15.0 IU/L | Standard Deviation 6.35 |
| Dapro 25 mg | Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Alkaline Phosphatase (Alk. Phosph) Levels in Blood at Indicated Time Points | AST; Day 43; n= 15, 20, 18, 21, 21 | 15.7 IU/L | Standard Deviation 6.31 |
| Dapro 25 mg | Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Alkaline Phosphatase (Alk. Phosph) Levels in Blood at Indicated Time Points | Alk. phosph.; Day 29; n= 17, 19, 18, 19,17 | 93.5 IU/L | Standard Deviation 42.92 |
| Dapro 25 mg | Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Alkaline Phosphatase (Alk. Phosph) Levels in Blood at Indicated Time Points | AST; Day 15; n= 17, 20, 18, 22, 20 | 15.4 IU/L | Standard Deviation 6.33 |
| Dapro 25 mg | Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Alkaline Phosphatase (Alk. Phosph) Levels in Blood at Indicated Time Points | ALT; Day 1; n= 18, 20, 20, 22, 22 | 10.7 IU/L | Standard Deviation 5.75 |
| Dapro 25 mg | Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Alkaline Phosphatase (Alk. Phosph) Levels in Blood at Indicated Time Points | ALT; Day 15; n= 17, 20, 18, 22, 20 | 11.9 IU/L | Standard Deviation 6.58 |
| Dapro 30 mg | Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Alkaline Phosphatase (Alk. Phosph) Levels in Blood at Indicated Time Points | Alk. phosph.; Day 43; n= 15, 20, 18, 21,21 | 108.6 IU/L | Standard Deviation 50.49 |
| Dapro 30 mg | Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Alkaline Phosphatase (Alk. Phosph) Levels in Blood at Indicated Time Points | Alk. phosph; Day 15; n= 17, 20, 18, 22,20 | 110.0 IU/L | Standard Deviation 62.65 |
| Dapro 30 mg | Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Alkaline Phosphatase (Alk. Phosph) Levels in Blood at Indicated Time Points | Alk. phosph.; Day 29; n= 17, 19, 18, 19,17 | 120.4 IU/L | Standard Deviation 67.51 |
| Dapro 30 mg | Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Alkaline Phosphatase (Alk. Phosph) Levels in Blood at Indicated Time Points | ALT; Day 29; n= 17, 19, 18, 19, 17 | 8.6 IU/L | Standard Deviation 3.12 |
| Dapro 30 mg | Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Alkaline Phosphatase (Alk. Phosph) Levels in Blood at Indicated Time Points | AST; Day 1; n= 18, 20, 20, 22, 22 | 13.6 IU/L | Standard Deviation 3.63 |
| Dapro 30 mg | Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Alkaline Phosphatase (Alk. Phosph) Levels in Blood at Indicated Time Points | ALT; Day 15; n= 17, 20, 18, 22, 20 | 8.4 IU/L | Standard Deviation 2.11 |
| Dapro 30 mg | Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Alkaline Phosphatase (Alk. Phosph) Levels in Blood at Indicated Time Points | ALT; Day 1; n= 18, 20, 20, 22, 22 | 11.5 IU/L | Standard Deviation 5.94 |
| Dapro 30 mg | Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Alkaline Phosphatase (Alk. Phosph) Levels in Blood at Indicated Time Points | Alk. phosph; Day 1; n= 18, 20, 20, 22, 22 | 115.4 IU/L | Standard Deviation 72.35 |
| Dapro 30 mg | Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Alkaline Phosphatase (Alk. Phosph) Levels in Blood at Indicated Time Points | AST; Day 15; n= 17, 20, 18, 22, 20 | 12.4 IU/L | Standard Deviation 2.89 |
| Dapro 30 mg | Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Alkaline Phosphatase (Alk. Phosph) Levels in Blood at Indicated Time Points | AST; Day 29; n= 17, 19, 18, 19, 17 | 13.5 IU/L | Standard Deviation 3.12 |
| Dapro 30 mg | Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Alkaline Phosphatase (Alk. Phosph) Levels in Blood at Indicated Time Points | ALT; Day 43; n= 15, 20, 18, 21, 21 | 11.2 IU/L | Standard Deviation 5.57 |
| Dapro 30 mg | Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Alkaline Phosphatase (Alk. Phosph) Levels in Blood at Indicated Time Points | AST; Day 43; n= 15, 20, 18, 21, 21 | 14.3 IU/L | Standard Deviation 4.76 |
Secondary
Albumin and Protein Levels in Blood at Indicated Tme Points
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Albumin and Protein Levels in Blood at Indicated Tme Points | Albumin; Day 1; n= 18, 20, 20, 22, 22 | 37.6 grams per liter (g/L) | Standard Deviation 2.89 |
| Placebo | Albumin and Protein Levels in Blood at Indicated Tme Points | Albumin; Day 43; n= 15, 20, 18, 21, 21 | 37.1 grams per liter (g/L) | Standard Deviation 2.85 |
| Placebo | Albumin and Protein Levels in Blood at Indicated Tme Points | Albumin; Day 15; n= 17, 20, 18, 22, 20 | 38.1 grams per liter (g/L) | Standard Deviation 2.68 |
| Placebo | Albumin and Protein Levels in Blood at Indicated Tme Points | Albumin; Day 29; n= 17, 19, 18, 19, 17 | 36.5 grams per liter (g/L) | Standard Deviation 3.22 |
| Placebo | Albumin and Protein Levels in Blood at Indicated Tme Points | Protein; Day 29; n= 17, 19, 18, 19, 17 | 66.1 grams per liter (g/L) | Standard Deviation 4.52 |
| Placebo | Albumin and Protein Levels in Blood at Indicated Tme Points | Protein; Day 43; n= 15, 20, 18, 21, 21 | 67.2 grams per liter (g/L) | Standard Deviation 4.25 |
| Placebo | Albumin and Protein Levels in Blood at Indicated Tme Points | Protein; Day 15; n= 17, 20, 18, 22, 20 | 68.1 grams per liter (g/L) | Standard Deviation 4.87 |
| Placebo | Albumin and Protein Levels in Blood at Indicated Tme Points | Protein; Day 1; n= 18, 20 ,20, 22, 22 | 67.3 grams per liter (g/L) | Standard Deviation 4.9 |
| Dapro 10 mg | Albumin and Protein Levels in Blood at Indicated Tme Points | Albumin; Day 29; n= 17, 19, 18, 19, 17 | 37.2 grams per liter (g/L) | Standard Deviation 3.26 |
| Dapro 10 mg | Albumin and Protein Levels in Blood at Indicated Tme Points | Albumin; Day 1; n= 18, 20, 20, 22, 22 | 38.6 grams per liter (g/L) | Standard Deviation 2.46 |
| Dapro 10 mg | Albumin and Protein Levels in Blood at Indicated Tme Points | Protein; Day 29; n= 17, 19, 18, 19, 17 | 65.7 grams per liter (g/L) | Standard Deviation 4.75 |
| Dapro 10 mg | Albumin and Protein Levels in Blood at Indicated Tme Points | Protein; Day 15; n= 17, 20, 18, 22, 20 | 66.5 grams per liter (g/L) | Standard Deviation 4.88 |
| Dapro 10 mg | Albumin and Protein Levels in Blood at Indicated Tme Points | Protein; Day 43; n= 15, 20, 18, 21, 21 | 67.4 grams per liter (g/L) | Standard Deviation 5.14 |
| Dapro 10 mg | Albumin and Protein Levels in Blood at Indicated Tme Points | Protein; Day 1; n= 18, 20 ,20, 22, 22 | 66.9 grams per liter (g/L) | Standard Deviation 5.42 |
| Dapro 10 mg | Albumin and Protein Levels in Blood at Indicated Tme Points | Albumin; Day 15; n= 17, 20, 18, 22, 20 | 38.1 grams per liter (g/L) | Standard Deviation 2.65 |
| Dapro 10 mg | Albumin and Protein Levels in Blood at Indicated Tme Points | Albumin; Day 43; n= 15, 20, 18, 21, 21 | 38.1 grams per liter (g/L) | Standard Deviation 3.02 |
| Dapro 15 mg | Albumin and Protein Levels in Blood at Indicated Tme Points | Albumin; Day 15; n= 17, 20, 18, 22, 20 | 38.4 grams per liter (g/L) | Standard Deviation 3.42 |
| Dapro 15 mg | Albumin and Protein Levels in Blood at Indicated Tme Points | Albumin; Day 29; n= 17, 19, 18, 19, 17 | 37.6 grams per liter (g/L) | Standard Deviation 3.62 |
| Dapro 15 mg | Albumin and Protein Levels in Blood at Indicated Tme Points | Protein; Day 1; n= 18, 20 ,20, 22, 22 | 67.4 grams per liter (g/L) | Standard Deviation 4.89 |
| Dapro 15 mg | Albumin and Protein Levels in Blood at Indicated Tme Points | Protein; Day 29; n= 17, 19, 18, 19, 17 | 66.0 grams per liter (g/L) | Standard Deviation 4.51 |
| Dapro 15 mg | Albumin and Protein Levels in Blood at Indicated Tme Points | Protein; Day 43; n= 15, 20, 18, 21, 21 | 66.8 grams per liter (g/L) | Standard Deviation 4.02 |
| Dapro 15 mg | Albumin and Protein Levels in Blood at Indicated Tme Points | Albumin; Day 1; n= 18, 20, 20, 22, 22 | 38.7 grams per liter (g/L) | Standard Deviation 3.84 |
| Dapro 15 mg | Albumin and Protein Levels in Blood at Indicated Tme Points | Albumin; Day 43; n= 15, 20, 18, 21, 21 | 37.9 grams per liter (g/L) | Standard Deviation 3.95 |
| Dapro 15 mg | Albumin and Protein Levels in Blood at Indicated Tme Points | Protein; Day 15; n= 17, 20, 18, 22, 20 | 67.3 grams per liter (g/L) | Standard Deviation 4.28 |
| Dapro 25 mg | Albumin and Protein Levels in Blood at Indicated Tme Points | Protein; Day 1; n= 18, 20 ,20, 22, 22 | 66.4 grams per liter (g/L) | Standard Deviation 5.16 |
| Dapro 25 mg | Albumin and Protein Levels in Blood at Indicated Tme Points | Protein; Day 15; n= 17, 20, 18, 22, 20 | 65.6 grams per liter (g/L) | Standard Deviation 5.13 |
| Dapro 25 mg | Albumin and Protein Levels in Blood at Indicated Tme Points | Protein; Day 29; n= 17, 19, 18, 19, 17 | 65.5 grams per liter (g/L) | Standard Deviation 6.5 |
| Dapro 25 mg | Albumin and Protein Levels in Blood at Indicated Tme Points | Protein; Day 43; n= 15, 20, 18, 21, 21 | 66.7 grams per liter (g/L) | Standard Deviation 7.7 |
| Dapro 25 mg | Albumin and Protein Levels in Blood at Indicated Tme Points | Albumin; Day 1; n= 18, 20, 20, 22, 22 | 38.8 grams per liter (g/L) | Standard Deviation 2.22 |
| Dapro 25 mg | Albumin and Protein Levels in Blood at Indicated Tme Points | Albumin; Day 15; n= 17, 20, 18, 22, 20 | 38.4 grams per liter (g/L) | Standard Deviation 2.52 |
| Dapro 25 mg | Albumin and Protein Levels in Blood at Indicated Tme Points | Albumin; Day 29; n= 17, 19, 18, 19, 17 | 37.4 grams per liter (g/L) | Standard Deviation 2.17 |
| Dapro 25 mg | Albumin and Protein Levels in Blood at Indicated Tme Points | Albumin; Day 43; n= 15, 20, 18, 21, 21 | 39.0 grams per liter (g/L) | Standard Deviation 3.11 |
| Dapro 30 mg | Albumin and Protein Levels in Blood at Indicated Tme Points | Albumin; Day 15; n= 17, 20, 18, 22, 20 | 37.2 grams per liter (g/L) | Standard Deviation 3.01 |
| Dapro 30 mg | Albumin and Protein Levels in Blood at Indicated Tme Points | Albumin; Day 1; n= 18, 20, 20, 22, 22 | 38.1 grams per liter (g/L) | Standard Deviation 3.52 |
| Dapro 30 mg | Albumin and Protein Levels in Blood at Indicated Tme Points | Protein; Day 43; n= 15, 20, 18, 21, 21 | 66.6 grams per liter (g/L) | Standard Deviation 6.34 |
| Dapro 30 mg | Albumin and Protein Levels in Blood at Indicated Tme Points | Albumin; Day 43; n= 15, 20, 18, 21, 21 | 37.5 grams per liter (g/L) | Standard Deviation 2.86 |
| Dapro 30 mg | Albumin and Protein Levels in Blood at Indicated Tme Points | Protein; Day 1; n= 18, 20 ,20, 22, 22 | 65.7 grams per liter (g/L) | Standard Deviation 4.65 |
| Dapro 30 mg | Albumin and Protein Levels in Blood at Indicated Tme Points | Protein; Day 29; n= 17, 19, 18, 19, 17 | 65.3 grams per liter (g/L) | Standard Deviation 5.3 |
| Dapro 30 mg | Albumin and Protein Levels in Blood at Indicated Tme Points | Protein; Day 15; n= 17, 20, 18, 22, 20 | 64.3 grams per liter (g/L) | Standard Deviation 4.7 |
| Dapro 30 mg | Albumin and Protein Levels in Blood at Indicated Tme Points | Albumin; Day 29; n= 17, 19, 18, 19, 17 | 36.9 grams per liter (g/L) | Standard Deviation 4.15 |
Secondary
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
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
Population: 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 | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | 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 | AUC (0-t); n= 19, 15, 16, 14 | 311.7 hour into nanograms/milliliter (h*ng/mL) | Geometric Coefficient of Variation 91.4 |
| Placebo | 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 | AUC (0-inf); n= 12, 9, 8, 11 | 348.2 hour into nanograms/milliliter (h*ng/mL) | Geometric Coefficient of Variation 78.2 |
| Dapro 10 mg | 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 | AUC (0-inf); n= 12, 9, 8, 11 | 383.5 hour into nanograms/milliliter (h*ng/mL) | Geometric Coefficient of Variation 142.7 |
| Dapro 10 mg | 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 | AUC (0-t); n= 19, 15, 16, 14 | 416.7 hour into nanograms/milliliter (h*ng/mL) | Geometric Coefficient of Variation 168.6 |
| Dapro 15 mg | 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 | AUC (0-t); n= 19, 15, 16, 14 | 513.9 hour into nanograms/milliliter (h*ng/mL) | Geometric Coefficient of Variation 396.1 |
| Dapro 15 mg | 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 | AUC (0-inf); n= 12, 9, 8, 11 | 1214 hour into nanograms/milliliter (h*ng/mL) | Geometric Coefficient of Variation 41.6 |
| Dapro 25 mg | 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 | AUC (0-t); n= 19, 15, 16, 14 | 1010 hour into nanograms/milliliter (h*ng/mL) | Geometric Coefficient of Variation 92.3 |
| Dapro 25 mg | 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 | AUC (0-inf); n= 12, 9, 8, 11 | 1369 hour into nanograms/milliliter (h*ng/mL) | Geometric Coefficient of Variation 59.3 |
Secondary
Bilirubin, Direct Bilirubin and Indirect Bilirubin Levels in Blood at Indicated Time Points
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Bilirubin, Direct Bilirubin and Indirect Bilirubin Levels in Blood at Indicated Time Points | Direct bilirubin; Day 43; n= 15, 20, 18, 21,21 | 1.3 Micromoles per liter (µmol/L) | Standard Deviation 1.23 |
| Placebo | Bilirubin, Direct Bilirubin and Indirect Bilirubin Levels in Blood at Indicated Time Points | Bilirubin; Day 1; n= 18, 20, 20, 22, 22 | 6.6 Micromoles per liter (µmol/L) | Standard Deviation 1.65 |
| Placebo | Bilirubin, Direct Bilirubin and Indirect Bilirubin Levels in Blood at Indicated Time Points | Indirect bilirubin; Day 43; n= 15, 20, 18, 21, 21 | 4.7 Micromoles per liter (µmol/L) | Standard Deviation 0.98 |
| Placebo | Bilirubin, Direct Bilirubin and Indirect Bilirubin Levels in Blood at Indicated Time Points | Bilirubin; Day 43; n= 15, 20 ,18, 21, 21 | 6.0 Micromoles per liter (µmol/L) | Standard Deviation 1.07 |
| Placebo | Bilirubin, Direct Bilirubin and Indirect Bilirubin Levels in Blood at Indicated Time Points | Direct bilirubin; Day 15; n= 17, 20, 18, 22, 20 | 1.5 Micromoles per liter (µmol/L) | Standard Deviation 1.66 |
| Placebo | Bilirubin, Direct Bilirubin and Indirect Bilirubin Levels in Blood at Indicated Time Points | Indirect bilirubin; Day 29; n= 17, 19, 18, 19, 17 | 4.4 Micromoles per liter (µmol/L) | Standard Deviation 2.03 |
| Placebo | Bilirubin, Direct Bilirubin and Indirect Bilirubin Levels in Blood at Indicated Time Points | Indirect bilirubin; Day 15; n= 17, 20, 18, 22, 20 | 5.2 Micromoles per liter (µmol/L) | Standard Deviation 2.01 |
| Placebo | Bilirubin, Direct Bilirubin and Indirect Bilirubin Levels in Blood at Indicated Time Points | Bilirubin; Day 29; n= 17, 19, 18, 19, 17 | 6.8 Micromoles per liter (µmol/L) | Standard Deviation 2.24 |
| Placebo | Bilirubin, Direct Bilirubin and Indirect Bilirubin Levels in Blood at Indicated Time Points | Direct bilirubin; Day 1; n= 18, 20, 20, 22, 22 | 1.8 Micromoles per liter (µmol/L) | Standard Deviation 1.17 |
| Placebo | Bilirubin, Direct Bilirubin and Indirect Bilirubin Levels in Blood at Indicated Time Points | Direct bilirubin; Day 29; n= 17, 19, 18, 19,17 | 2.5 Micromoles per liter (µmol/L) | Standard Deviation 2.29 |
| Placebo | Bilirubin, Direct Bilirubin and Indirect Bilirubin Levels in Blood at Indicated Time Points | Bilirubin; Day 15; n= 17, 20, 18, 22, 20 | 6.7 Micromoles per liter (µmol/L) | Standard Deviation 3.08 |
| Placebo | Bilirubin, Direct Bilirubin and Indirect Bilirubin Levels in Blood at Indicated Time Points | Indirect bilirubin; Day 1; n= 18, 20, 20, 22, 22 | 4.8 Micromoles per liter (µmol/L) | Standard Deviation 1.22 |
| Dapro 10 mg | Bilirubin, Direct Bilirubin and Indirect Bilirubin Levels in Blood at Indicated Time Points | Indirect bilirubin; Day 29; n= 17, 19, 18, 19, 17 | 5.4 Micromoles per liter (µmol/L) | Standard Deviation 1.64 |
| Dapro 10 mg | Bilirubin, Direct Bilirubin and Indirect Bilirubin Levels in Blood at Indicated Time Points | Direct bilirubin; Day 15; n= 17, 20, 18, 22, 20 | 2.2 Micromoles per liter (µmol/L) | Standard Deviation 0.62 |
| Dapro 10 mg | Bilirubin, Direct Bilirubin and Indirect Bilirubin Levels in Blood at Indicated Time Points | Bilirubin; Day 15; n= 17, 20, 18, 22, 20 | 7.1 Micromoles per liter (µmol/L) | Standard Deviation 2.29 |
| Dapro 10 mg | Bilirubin, Direct Bilirubin and Indirect Bilirubin Levels in Blood at Indicated Time Points | Direct bilirubin; Day 29; n= 17, 19, 18, 19,17 | 1.6 Micromoles per liter (µmol/L) | Standard Deviation 1.07 |
| Dapro 10 mg | Bilirubin, Direct Bilirubin and Indirect Bilirubin Levels in Blood at Indicated Time Points | Bilirubin; Day 1; n= 18, 20, 20, 22, 22 | 7.8 Micromoles per liter (µmol/L) | Standard Deviation 3.11 |
| Dapro 10 mg | Bilirubin, Direct Bilirubin and Indirect Bilirubin Levels in Blood at Indicated Time Points | Indirect bilirubin; Day 15; n= 17, 20, 18, 22, 20 | 4.9 Micromoles per liter (µmol/L) | Standard Deviation 2.1 |
| Dapro 10 mg | Bilirubin, Direct Bilirubin and Indirect Bilirubin Levels in Blood at Indicated Time Points | Bilirubin; Day 29; n= 17, 19, 18, 19, 17 | 6.9 Micromoles per liter (µmol/L) | Standard Deviation 1.93 |
| Dapro 10 mg | Bilirubin, Direct Bilirubin and Indirect Bilirubin Levels in Blood at Indicated Time Points | Direct bilirubin; Day 43; n= 15, 20, 18, 21,21 | 1.9 Micromoles per liter (µmol/L) | Standard Deviation 0.45 |
| Dapro 10 mg | Bilirubin, Direct Bilirubin and Indirect Bilirubin Levels in Blood at Indicated Time Points | Indirect bilirubin; Day 43; n= 15, 20, 18, 21, 21 | 5.1 Micromoles per liter (µmol/L) | Standard Deviation 2.38 |
| Dapro 10 mg | Bilirubin, Direct Bilirubin and Indirect Bilirubin Levels in Blood at Indicated Time Points | Bilirubin; Day 43; n= 15, 20 ,18, 21, 21 | 7.0 Micromoles per liter (µmol/L) | Standard Deviation 2.38 |
| Dapro 10 mg | Bilirubin, Direct Bilirubin and Indirect Bilirubin Levels in Blood at Indicated Time Points | Indirect bilirubin; Day 1; n= 18, 20, 20, 22, 22 | 5.9 Micromoles per liter (µmol/L) | Standard Deviation 2.94 |
| Dapro 10 mg | Bilirubin, Direct Bilirubin and Indirect Bilirubin Levels in Blood at Indicated Time Points | Direct bilirubin; Day 1; n= 18, 20, 20, 22, 22 | 1.9 Micromoles per liter (µmol/L) | Standard Deviation 0.79 |
| Dapro 15 mg | Bilirubin, Direct Bilirubin and Indirect Bilirubin Levels in Blood at Indicated Time Points | Indirect bilirubin; Day 15; n= 17, 20, 18, 22, 20 | 4.8 Micromoles per liter (µmol/L) | Standard Deviation 1.83 |
| Dapro 15 mg | Bilirubin, Direct Bilirubin and Indirect Bilirubin Levels in Blood at Indicated Time Points | Bilirubin; Day 1; n= 18, 20, 20, 22, 22 | 6.6 Micromoles per liter (µmol/L) | Standard Deviation 1.31 |
| Dapro 15 mg | Bilirubin, Direct Bilirubin and Indirect Bilirubin Levels in Blood at Indicated Time Points | Bilirubin; Day 15; n= 17, 20, 18, 22, 20 | 7.2 Micromoles per liter (µmol/L) | Standard Deviation 2.67 |
| Dapro 15 mg | Bilirubin, Direct Bilirubin and Indirect Bilirubin Levels in Blood at Indicated Time Points | Bilirubin; Day 29; n= 17, 19, 18, 19, 17 | 7.6 Micromoles per liter (µmol/L) | Standard Deviation 2.12 |
| Dapro 15 mg | Bilirubin, Direct Bilirubin and Indirect Bilirubin Levels in Blood at Indicated Time Points | Bilirubin; Day 43; n= 15, 20 ,18, 21, 21 | 7.2 Micromoles per liter (µmol/L) | Standard Deviation 2.07 |
| Dapro 15 mg | Bilirubin, Direct Bilirubin and Indirect Bilirubin Levels in Blood at Indicated Time Points | Direct bilirubin; Day 1; n= 18, 20, 20, 22, 22 | 2.0 Micromoles per liter (µmol/L) | Standard Deviation 1.12 |
| Dapro 15 mg | Bilirubin, Direct Bilirubin and Indirect Bilirubin Levels in Blood at Indicated Time Points | Direct bilirubin; Day 15; n= 17, 20, 18, 22, 20 | 2.4 Micromoles per liter (µmol/L) | Standard Deviation 1.29 |
| Dapro 15 mg | Bilirubin, Direct Bilirubin and Indirect Bilirubin Levels in Blood at Indicated Time Points | Direct bilirubin; Day 29; n= 17, 19, 18, 19,17 | 2.7 Micromoles per liter (µmol/L) | Standard Deviation 0.97 |
| Dapro 15 mg | Bilirubin, Direct Bilirubin and Indirect Bilirubin Levels in Blood at Indicated Time Points | Direct bilirubin; Day 43; n= 15, 20, 18, 21,21 | 2.3 Micromoles per liter (µmol/L) | Standard Deviation 0.77 |
| Dapro 15 mg | Bilirubin, Direct Bilirubin and Indirect Bilirubin Levels in Blood at Indicated Time Points | Indirect bilirubin; Day 1; n= 18, 20, 20, 22, 22 | 4.6 Micromoles per liter (µmol/L) | Standard Deviation 0.94 |
| Dapro 15 mg | Bilirubin, Direct Bilirubin and Indirect Bilirubin Levels in Blood at Indicated Time Points | Indirect bilirubin; Day 29; n= 17, 19, 18, 19, 17 | 4.9 Micromoles per liter (µmol/L) | Standard Deviation 1.57 |
| Dapro 15 mg | Bilirubin, Direct Bilirubin and Indirect Bilirubin Levels in Blood at Indicated Time Points | Indirect bilirubin; Day 43; n= 15, 20, 18, 21, 21 | 4.9 Micromoles per liter (µmol/L) | Standard Deviation 1.41 |
| Dapro 25 mg | Bilirubin, Direct Bilirubin and Indirect Bilirubin Levels in Blood at Indicated Time Points | Direct bilirubin; Day 43; n= 15, 20, 18, 21,21 | 1.7 Micromoles per liter (µmol/L) | Standard Deviation 0.72 |
| Dapro 25 mg | Bilirubin, Direct Bilirubin and Indirect Bilirubin Levels in Blood at Indicated Time Points | Bilirubin; Day 1; n= 18, 20, 20, 22, 22 | 6.5 Micromoles per liter (µmol/L) | Standard Deviation 1.1 |
| Dapro 25 mg | Bilirubin, Direct Bilirubin and Indirect Bilirubin Levels in Blood at Indicated Time Points | Bilirubin; Day 29; n= 17, 19, 18, 19, 17 | 6.5 Micromoles per liter (µmol/L) | Standard Deviation 1.47 |
| Dapro 25 mg | Bilirubin, Direct Bilirubin and Indirect Bilirubin Levels in Blood at Indicated Time Points | Indirect bilirubin; Day 1; n= 18, 20, 20, 22, 22 | 4.6 Micromoles per liter (µmol/L) | Standard Deviation 1.14 |
| Dapro 25 mg | Bilirubin, Direct Bilirubin and Indirect Bilirubin Levels in Blood at Indicated Time Points | Bilirubin; Day 15; n= 17, 20, 18, 22, 20 | 6.5 Micromoles per liter (µmol/L) | Standard Deviation 1.1 |
| Dapro 25 mg | Bilirubin, Direct Bilirubin and Indirect Bilirubin Levels in Blood at Indicated Time Points | Direct bilirubin; Day 1; n= 18, 20, 20, 22, 22 | 1.9 Micromoles per liter (µmol/L) | Standard Deviation 0.75 |
| Dapro 25 mg | Bilirubin, Direct Bilirubin and Indirect Bilirubin Levels in Blood at Indicated Time Points | Indirect bilirubin; Day 15; n= 17, 20, 18, 22, 20 | 4.7 Micromoles per liter (µmol/L) | Standard Deviation 0.98 |
| Dapro 25 mg | Bilirubin, Direct Bilirubin and Indirect Bilirubin Levels in Blood at Indicated Time Points | Bilirubin; Day 43; n= 15, 20 ,18, 21, 21 | 6.5 Micromoles per liter (µmol/L) | Standard Deviation 1.25 |
| Dapro 25 mg | Bilirubin, Direct Bilirubin and Indirect Bilirubin Levels in Blood at Indicated Time Points | Indirect bilirubin; Day 43; n= 15, 20, 18, 21, 21 | 4.8 Micromoles per liter (µmol/L) | Standard Deviation 1.48 |
| Dapro 25 mg | Bilirubin, Direct Bilirubin and Indirect Bilirubin Levels in Blood at Indicated Time Points | Direct bilirubin; Day 29; n= 17, 19, 18, 19,17 | 1.8 Micromoles per liter (µmol/L) | Standard Deviation 0.63 |
| Dapro 25 mg | Bilirubin, Direct Bilirubin and Indirect Bilirubin Levels in Blood at Indicated Time Points | Indirect bilirubin; Day 29; n= 17, 19, 18, 19, 17 | 4.7 Micromoles per liter (µmol/L) | Standard Deviation 1.52 |
| Dapro 25 mg | Bilirubin, Direct Bilirubin and Indirect Bilirubin Levels in Blood at Indicated Time Points | Direct bilirubin; Day 15; n= 17, 20, 18, 22, 20 | 1.8 Micromoles per liter (µmol/L) | Standard Deviation 0.85 |
| Dapro 30 mg | Bilirubin, Direct Bilirubin and Indirect Bilirubin Levels in Blood at Indicated Time Points | Indirect bilirubin; Day 29; n= 17, 19, 18, 19, 17 | 5.4 Micromoles per liter (µmol/L) | Standard Deviation 1.7 |
| Dapro 30 mg | Bilirubin, Direct Bilirubin and Indirect Bilirubin Levels in Blood at Indicated Time Points | Bilirubin; Day 1; n= 18, 20, 20, 22, 22 | 7.2 Micromoles per liter (µmol/L) | Standard Deviation 2.44 |
| Dapro 30 mg | Bilirubin, Direct Bilirubin and Indirect Bilirubin Levels in Blood at Indicated Time Points | Direct bilirubin; Day 43; n= 15, 20, 18, 21,21 | 2.3 Micromoles per liter (µmol/L) | Standard Deviation 1.31 |
| Dapro 30 mg | Bilirubin, Direct Bilirubin and Indirect Bilirubin Levels in Blood at Indicated Time Points | Bilirubin; Day 43; n= 15, 20 ,18, 21, 21 | 7.5 Micromoles per liter (µmol/L) | Standard Deviation 2.44 |
| Dapro 30 mg | Bilirubin, Direct Bilirubin and Indirect Bilirubin Levels in Blood at Indicated Time Points | Indirect bilirubin; Day 1; n= 18, 20, 20, 22, 22 | 4.8 Micromoles per liter (µmol/L) | Standard Deviation 1.92 |
| Dapro 30 mg | Bilirubin, Direct Bilirubin and Indirect Bilirubin Levels in Blood at Indicated Time Points | Direct bilirubin; Day 1; n= 18, 20, 20, 22, 22 | 2.4 Micromoles per liter (µmol/L) | Standard Deviation 1.33 |
| Dapro 30 mg | Bilirubin, Direct Bilirubin and Indirect Bilirubin Levels in Blood at Indicated Time Points | Bilirubin; Day 29; n= 17, 19, 18, 19, 17 | 7.8 Micromoles per liter (µmol/L) | Standard Deviation 2.44 |
| Dapro 30 mg | Bilirubin, Direct Bilirubin and Indirect Bilirubin Levels in Blood at Indicated Time Points | Bilirubin; Day 15; n= 17, 20, 18, 22, 20 | 7.8 Micromoles per liter (µmol/L) | Standard Deviation 2.24 |
| Dapro 30 mg | Bilirubin, Direct Bilirubin and Indirect Bilirubin Levels in Blood at Indicated Time Points | Indirect bilirubin; Day 43; n= 15, 20, 18, 21, 21 | 5.2 Micromoles per liter (µmol/L) | Standard Deviation 1.73 |
| Dapro 30 mg | Bilirubin, Direct Bilirubin and Indirect Bilirubin Levels in Blood at Indicated Time Points | Direct bilirubin; Day 15; n= 17, 20, 18, 22, 20 | 2.6 Micromoles per liter (µmol/L) | Standard Deviation 1.14 |
| Dapro 30 mg | Bilirubin, Direct Bilirubin and Indirect Bilirubin Levels in Blood at Indicated Time Points | Indirect bilirubin; Day 15; n= 17, 20, 18, 22, 20 | 5.2 Micromoles per liter (µmol/L) | Standard Deviation 1.77 |
| Dapro 30 mg | Bilirubin, Direct Bilirubin and Indirect Bilirubin Levels in Blood at Indicated Time Points | Direct bilirubin; Day 29; n= 17, 19, 18, 19,17 | 2.4 Micromoles per liter (µmol/L) | Standard Deviation 1.46 |
Secondary
Change From Baseline in Albumin and Protein Levels
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Albumin and Protein Levels | Albumin; Day 15; n= 17, 20, 18, 22, 20 | 0.8 g/L | Standard Deviation 1.6 |
| Placebo | Change From Baseline in Albumin and Protein Levels | Albumin; Day 29; n= 17, 19, 18, 19, 17 | -0.5 g/L | Standard Deviation 2.24 |
| Placebo | Change From Baseline in Albumin and Protein Levels | Albumin; Day 43; n= 15, 20, 18, 21, 21 | 0.1 g/L | Standard Deviation 2 |
| Placebo | Change From Baseline in Albumin and Protein Levels | Protein; Day 15; n= 17, 20, 18, 22, 20 | 0.8 g/L | Standard Deviation 2.97 |
| Placebo | Change From Baseline in Albumin and Protein Levels | Protein; Day 29; n= 17, 19, 18, 19, 17 | -1.1 g/L | Standard Deviation 4.26 |
| Placebo | Change From Baseline in Albumin and Protein Levels | Protein; Day 43; n= 15, 20, 18, 21, 21 | -0.1 g/L | Standard Deviation 4.19 |
| Dapro 10 mg | Change From Baseline in Albumin and Protein Levels | Protein; Day 29; n= 17, 19, 18, 19, 17 | -0.8 g/L | Standard Deviation 3.82 |
| Dapro 10 mg | Change From Baseline in Albumin and Protein Levels | Protein; Day 43; n= 15, 20, 18, 21, 21 | 0.6 g/L | Standard Deviation 4.38 |
| Dapro 10 mg | Change From Baseline in Albumin and Protein Levels | Albumin; Day 15; n= 17, 20, 18, 22, 20 | -0.5 g/L | Standard Deviation 1.64 |
| Dapro 10 mg | Change From Baseline in Albumin and Protein Levels | Albumin; Day 43; n= 15, 20, 18, 21, 21 | -0.6 g/L | Standard Deviation 2.14 |
| Dapro 10 mg | Change From Baseline in Albumin and Protein Levels | Protein; Day 15; n= 17, 20, 18, 22, 20 | -0.4 g/L | Standard Deviation 3.25 |
| Dapro 10 mg | Change From Baseline in Albumin and Protein Levels | Albumin; Day 29; n= 17, 19, 18, 19, 17 | -1.3 g/L | Standard Deviation 2.03 |
| Dapro 15 mg | Change From Baseline in Albumin and Protein Levels | Protein; Day 15; n= 17, 20, 18, 22, 20 | 0.3 g/L | Standard Deviation 3.65 |
| Dapro 15 mg | Change From Baseline in Albumin and Protein Levels | Protein; Day 29; n= 17, 19, 18, 19, 17 | -1.2 g/L | Standard Deviation 2.9 |
| Dapro 15 mg | Change From Baseline in Albumin and Protein Levels | Albumin; Day 15; n= 17, 20, 18, 22, 20 | 0.2 g/L | Standard Deviation 2.24 |
| Dapro 15 mg | Change From Baseline in Albumin and Protein Levels | Albumin; Day 43; n= 15, 20, 18, 21, 21 | -0.7 g/L | Standard Deviation 2.22 |
| Dapro 15 mg | Change From Baseline in Albumin and Protein Levels | Albumin; Day 29; n= 17, 19, 18, 19, 17 | -0.7 g/L | Standard Deviation 2 |
| Dapro 15 mg | Change From Baseline in Albumin and Protein Levels | Protein; Day 43; n= 15, 20, 18, 21, 21 | -0.9 g/L | Standard Deviation 3.17 |
| Dapro 25 mg | Change From Baseline in Albumin and Protein Levels | Protein; Day 15; n= 17, 20, 18, 22, 20 | -0.7 g/L | Standard Deviation 2.35 |
| Dapro 25 mg | Change From Baseline in Albumin and Protein Levels | Albumin; Day 29; n= 17, 19, 18, 19, 17 | -1.3 g/L | Standard Deviation 1.85 |
| Dapro 25 mg | Change From Baseline in Albumin and Protein Levels | Albumin; Day 43; n= 15, 20, 18, 21, 21 | 0.1 g/L | Standard Deviation 3.85 |
| Dapro 25 mg | Change From Baseline in Albumin and Protein Levels | Protein; Day 43; n= 15, 20, 18, 21, 21 | 0.3 g/L | Standard Deviation 4.84 |
| Dapro 25 mg | Change From Baseline in Albumin and Protein Levels | Protein; Day 29; n= 17, 19, 18, 19, 17 | -1.0 g/L | Standard Deviation 3.28 |
| Dapro 25 mg | Change From Baseline in Albumin and Protein Levels | Albumin; Day 15; n= 17, 20, 18, 22, 20 | -0.5 g/L | Standard Deviation 1.44 |
| Dapro 30 mg | Change From Baseline in Albumin and Protein Levels | Protein; Day 29; n= 17, 19, 18, 19, 17 | 0.1 g/L | Standard Deviation 2.56 |
| Dapro 30 mg | Change From Baseline in Albumin and Protein Levels | Albumin; Day 43; n= 15, 20, 18, 21, 21 | -0.3 g/L | Standard Deviation 1.74 |
| Dapro 30 mg | Change From Baseline in Albumin and Protein Levels | Albumin; Day 29; n= 17, 19, 18, 19, 17 | -0.9 g/L | Standard Deviation 1.76 |
| Dapro 30 mg | Change From Baseline in Albumin and Protein Levels | Protein; Day 43; n= 15, 20, 18, 21, 21 | 1.2 g/L | Standard Deviation 3.95 |
| Dapro 30 mg | Change From Baseline in Albumin and Protein Levels | Protein; Day 15; n= 17, 20, 18, 22, 20 | -1.5 g/L | Standard Deviation 3.03 |
| Dapro 30 mg | Change From Baseline in Albumin and Protein Levels | Albumin; Day 15; n= 17, 20, 18, 22, 20 | -1.0 g/L | Standard Deviation 2.34 |
Secondary
Change From Baseline in ALT, AST, Alk. Phosph. Levels
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in ALT, AST, Alk. Phosph. Levels | Alk.phosph.; Day 43; n= 15, 20, 18, 21, 21 | -1.5 IU/L | Standard Deviation 17.01 |
| Placebo | Change From Baseline in ALT, AST, Alk. Phosph. Levels | AST; Day 29; n= 17, 19, 18, 19, 17 | 11.5 IU/L | Standard Deviation 30.64 |
| Placebo | Change From Baseline in ALT, AST, Alk. Phosph. Levels | ALT; Day 29; n= 17, 19, 18, 19, 17 | 11.8 IU/L | Standard Deviation 32.39 |
| Placebo | Change From Baseline in ALT, AST, Alk. Phosph. Levels | AST; Day 43; n= 15, 20, 18, 21, 21 | 0.6 IU/L | Standard Deviation 3.94 |
| Placebo | Change From Baseline in ALT, AST, Alk. Phosph. Levels | Alk.phosph.; Day 29; n= 17, 19, 18, 19, 17 | -0.4 IU/L | Standard Deviation 19.31 |
| Placebo | Change From Baseline in ALT, AST, Alk. Phosph. Levels | ALT; Day 43; n= 15, 20, 18, 21, 21 | 0.9 IU/L | Standard Deviation 4.32 |
| Placebo | Change From Baseline in ALT, AST, Alk. Phosph. Levels | Alk.phosph.; Day 15; n= 17, 20, 18, 22, 20 | 3.2 IU/L | Standard Deviation 10.28 |
| Placebo | Change From Baseline in ALT, AST, Alk. Phosph. Levels | AST; Day 15; n= 17, 20, 18, 22, 20 | 2.3 IU/L | Standard Deviation 5.7 |
| Placebo | Change From Baseline in ALT, AST, Alk. Phosph. Levels | ALT; Day 15; n= 17, 20, 18, 22, 20 | 3.6 IU/L | Standard Deviation 9.59 |
| Dapro 10 mg | Change From Baseline in ALT, AST, Alk. Phosph. Levels | Alk.phosph.; Day 15; n= 17, 20, 18, 22, 20 | 3.2 IU/L | Standard Deviation 16.13 |
| Dapro 10 mg | Change From Baseline in ALT, AST, Alk. Phosph. Levels | AST; Day 43; n= 15, 20, 18, 21, 21 | 0.7 IU/L | Standard Deviation 2.49 |
| Dapro 10 mg | Change From Baseline in ALT, AST, Alk. Phosph. Levels | AST; Day 15; n= 17, 20, 18, 22, 20 | 0.1 IU/L | Standard Deviation 2.45 |
| Dapro 10 mg | Change From Baseline in ALT, AST, Alk. Phosph. Levels | AST; Day 29; n= 17, 19, 18, 19, 17 | -0.3 IU/L | Standard Deviation 3.3 |
| Dapro 10 mg | Change From Baseline in ALT, AST, Alk. Phosph. Levels | ALT; Day 43; n= 15, 20, 18, 21, 21 | 0.4 IU/L | Standard Deviation 5.29 |
| Dapro 10 mg | Change From Baseline in ALT, AST, Alk. Phosph. Levels | Alk.phosph.; Day 43; n= 15, 20, 18, 21, 21 | 5.4 IU/L | Standard Deviation 21.34 |
| Dapro 10 mg | Change From Baseline in ALT, AST, Alk. Phosph. Levels | ALT; Day 29; n= 17, 19, 18, 19, 17 | -0.9 IU/L | Standard Deviation 4.65 |
| Dapro 10 mg | Change From Baseline in ALT, AST, Alk. Phosph. Levels | ALT; Day 15; n= 17, 20, 18, 22, 20 | 0.5 IU/L | Standard Deviation 5.65 |
| Dapro 10 mg | Change From Baseline in ALT, AST, Alk. Phosph. Levels | Alk.phosph.; Day 29; n= 17, 19, 18, 19, 17 | 5.1 IU/L | Standard Deviation 19.09 |
| Dapro 15 mg | Change From Baseline in ALT, AST, Alk. Phosph. Levels | AST; Day 43; n= 15, 20, 18, 21, 21 | -0.6 IU/L | Standard Deviation 7.99 |
| Dapro 15 mg | Change From Baseline in ALT, AST, Alk. Phosph. Levels | ALT; Day 15; n= 17, 20, 18, 22, 20 | -3.1 IU/L | Standard Deviation 5.53 |
| Dapro 15 mg | Change From Baseline in ALT, AST, Alk. Phosph. Levels | ALT; Day 29; n= 17, 19, 18, 19, 17 | -3.4 IU/L | Standard Deviation 9.83 |
| Dapro 15 mg | Change From Baseline in ALT, AST, Alk. Phosph. Levels | ALT; Day 43; n= 15, 20, 18, 21, 21 | -2.5 IU/L | Standard Deviation 8.97 |
| Dapro 15 mg | Change From Baseline in ALT, AST, Alk. Phosph. Levels | AST; Day 15; n= 17, 20, 18, 22, 20 | -2.7 IU/L | Standard Deviation 6.29 |
| Dapro 15 mg | Change From Baseline in ALT, AST, Alk. Phosph. Levels | AST; Day 29; n= 17, 19, 18, 19, 17 | -1.8 IU/L | Standard Deviation 5.6 |
| Dapro 15 mg | Change From Baseline in ALT, AST, Alk. Phosph. Levels | Alk.phosph.; Day 15; n= 17, 20, 18, 22, 20 | 2.7 IU/L | Standard Deviation 29.73 |
| Dapro 15 mg | Change From Baseline in ALT, AST, Alk. Phosph. Levels | Alk.phosph.; Day 29; n= 17, 19, 18, 19, 17 | -0.9 IU/L | Standard Deviation 30.13 |
| Dapro 15 mg | Change From Baseline in ALT, AST, Alk. Phosph. Levels | Alk.phosph.; Day 43; n= 15, 20, 18, 21, 21 | 2.7 IU/L | Standard Deviation 31.96 |
| Dapro 25 mg | Change From Baseline in ALT, AST, Alk. Phosph. Levels | AST; Day 15; n= 17, 20, 18, 22, 20 | 1.0 IU/L | Standard Deviation 5.26 |
| Dapro 25 mg | Change From Baseline in ALT, AST, Alk. Phosph. Levels | AST; Day 43; n= 15, 20, 18, 21, 21 | 1.5 IU/L | Standard Deviation 3.71 |
| Dapro 25 mg | Change From Baseline in ALT, AST, Alk. Phosph. Levels | ALT; Day 43; n= 15, 20, 18, 21, 21 | 2.2 IU/L | Standard Deviation 4.08 |
| Dapro 25 mg | Change From Baseline in ALT, AST, Alk. Phosph. Levels | Alk.phosph.; Day 15; n= 17, 20, 18, 22, 20 | 2.1 IU/L | Standard Deviation 17.23 |
| Dapro 25 mg | Change From Baseline in ALT, AST, Alk. Phosph. Levels | ALT; Day 29; n= 17, 19, 18, 19, 17 | -0.2 IU/L | Standard Deviation 3.87 |
| Dapro 25 mg | Change From Baseline in ALT, AST, Alk. Phosph. Levels | Alk.phosph.; Day 43; n= 15, 20, 18, 21, 21 | 18.0 IU/L | Standard Deviation 66.44 |
| Dapro 25 mg | Change From Baseline in ALT, AST, Alk. Phosph. Levels | Alk.phosph.; Day 29; n= 17, 19, 18, 19, 17 | 0.9 IU/L | Standard Deviation 13.47 |
| Dapro 25 mg | Change From Baseline in ALT, AST, Alk. Phosph. Levels | ALT; Day 15; n= 17, 20, 18, 22, 20 | 1.1 IU/L | Standard Deviation 4.79 |
| Dapro 25 mg | Change From Baseline in ALT, AST, Alk. Phosph. Levels | AST; Day 29; n= 17, 19, 18, 19, 17 | 0.9 IU/L | Standard Deviation 3.6 |
| Dapro 30 mg | Change From Baseline in ALT, AST, Alk. Phosph. Levels | ALT; Day 15; n= 17, 20, 18, 22, 20 | -3.4 IU/L | Standard Deviation 5.52 |
| Dapro 30 mg | Change From Baseline in ALT, AST, Alk. Phosph. Levels | AST; Day 15; n= 17, 20, 18, 22, 20 | -1.6 IU/L | Standard Deviation 3.32 |
| Dapro 30 mg | Change From Baseline in ALT, AST, Alk. Phosph. Levels | AST; Day 43; n= 15, 20, 18, 21, 21 | 0.7 IU/L | Standard Deviation 3.41 |
| Dapro 30 mg | Change From Baseline in ALT, AST, Alk. Phosph. Levels | ALT; Day 43; n= 15, 20, 18, 21, 21 | -0.4 IU/L | Standard Deviation 3.69 |
| Dapro 30 mg | Change From Baseline in ALT, AST, Alk. Phosph. Levels | AST; Day 29; n= 17, 19, 18, 19, 17 | -0.3 IU/L | Standard Deviation 3.67 |
| Dapro 30 mg | Change From Baseline in ALT, AST, Alk. Phosph. Levels | Alk.phosph.; Day 43; n= 15, 20, 18, 21, 21 | -8.4 IU/L | Standard Deviation 56.06 |
| Dapro 30 mg | Change From Baseline in ALT, AST, Alk. Phosph. Levels | Alk.phosph.; Day 29; n= 17, 19, 18, 19, 17 | -1.2 IU/L | Standard Deviation 28.6 |
| Dapro 30 mg | Change From Baseline in ALT, AST, Alk. Phosph. Levels | Alk.phosph.; Day 15; n= 17, 20, 18, 22, 20 | -4.7 IU/L | Standard Deviation 18.9 |
| Dapro 30 mg | Change From Baseline in ALT, AST, Alk. Phosph. Levels | ALT; Day 29; n= 17, 19, 18, 19, 17 | -3.6 IU/L | Standard Deviation 4.72 |
Secondary
Change From Baseline in Bilirubin, Direct Bilirubin, Indirect Bilirubin Levels
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Bilirubin, Direct Bilirubin, Indirect Bilirubin Levels | Indirect bilirubin; Day 43; n= 15, 20, 18, 21, 21 | 0.0 µmol/L | Standard Deviation 1.07 |
| Placebo | Change From Baseline in Bilirubin, Direct Bilirubin, Indirect Bilirubin Levels | Direct bilirubin; Day 29; n= 17, 19, 18, 19, 17 | 0.7 µmol/L | Standard Deviation 1.86 |
| Placebo | Change From Baseline in Bilirubin, Direct Bilirubin, Indirect Bilirubin Levels | Bilirubin; Day 29; n= 17, 19, 18, 19, 17 | 0.2 µmol/L | Standard Deviation 0.97 |
| Placebo | Change From Baseline in Bilirubin, Direct Bilirubin, Indirect Bilirubin Levels | Direct bilirubin; Day 43; n= 15, 20, 18, 21, 21 | -0.1 µmol/L | Standard Deviation 1.19 |
| Placebo | Change From Baseline in Bilirubin, Direct Bilirubin, Indirect Bilirubin Levels | Indirect bilirubin; Day 29; n= 17, 19, 18, 19, 17 | -0.5 µmol/L | Standard Deviation 1.66 |
| Placebo | Change From Baseline in Bilirubin, Direct Bilirubin, Indirect Bilirubin Levels | Bilirubin; Day 43; n= 15, 20, 18, 21, 21 | -0.1 µmol/L | Standard Deviation 0.52 |
| Placebo | Change From Baseline in Bilirubin, Direct Bilirubin, Indirect Bilirubin Levels | Indirect bilirubin; Day 15; n= 17, 20, 18, 22, 20 | 0.4 µmol/L | Standard Deviation 1.46 |
| Placebo | Change From Baseline in Bilirubin, Direct Bilirubin, Indirect Bilirubin Levels | Direct bilirubin; Day 15; n= 17, 20, 18, 22, 20 | -0.1 µmol/L | Standard Deviation 1.11 |
| Placebo | Change From Baseline in Bilirubin, Direct Bilirubin, Indirect Bilirubin Levels | Bilirubin; Day 15; n= 17, 20, 18, 22, 20 | 0.2 µmol/L | Standard Deviation 1.56 |
| Dapro 10 mg | Change From Baseline in Bilirubin, Direct Bilirubin, Indirect Bilirubin Levels | Indirect bilirubin; Day 15; n= 17, 20, 18, 22, 20 | -1.0 µmol/L | Standard Deviation 1.38 |
| Dapro 10 mg | Change From Baseline in Bilirubin, Direct Bilirubin, Indirect Bilirubin Levels | Direct bilirubin; Day 43; n= 15, 20, 18, 21, 21 | 0.0 µmol/L | Standard Deviation 0.92 |
| Dapro 10 mg | Change From Baseline in Bilirubin, Direct Bilirubin, Indirect Bilirubin Levels | Direct bilirubin; Day 15; n= 17, 20, 18, 22, 20 | 0.3 µmol/L | Standard Deviation 0.73 |
| Dapro 10 mg | Change From Baseline in Bilirubin, Direct Bilirubin, Indirect Bilirubin Levels | Direct bilirubin; Day 29; n= 17, 19, 18, 19, 17 | -0.3 µmol/L | Standard Deviation 1 |
| Dapro 10 mg | Change From Baseline in Bilirubin, Direct Bilirubin, Indirect Bilirubin Levels | Bilirubin; Day 43; n= 15, 20, 18, 21, 21 | -0.8 µmol/L | Standard Deviation 1.51 |
| Dapro 10 mg | Change From Baseline in Bilirubin, Direct Bilirubin, Indirect Bilirubin Levels | Indirect bilirubin; Day 43; n= 15, 20, 18, 21, 21 | -0.8 µmol/L | Standard Deviation 1.64 |
| Dapro 10 mg | Change From Baseline in Bilirubin, Direct Bilirubin, Indirect Bilirubin Levels | Bilirubin; Day 29; n= 17, 19, 18, 19, 17 | -0.3 µmol/L | Standard Deviation 1.2 |
| Dapro 10 mg | Change From Baseline in Bilirubin, Direct Bilirubin, Indirect Bilirubin Levels | Bilirubin; Day 15; n= 17, 20, 18, 22, 20 | -0.7 µmol/L | Standard Deviation 1.49 |
| Dapro 10 mg | Change From Baseline in Bilirubin, Direct Bilirubin, Indirect Bilirubin Levels | Indirect bilirubin; Day 29; n= 17, 19, 18, 19, 17 | 0.0 µmol/L | Standard Deviation 1.15 |
| Dapro 15 mg | Change From Baseline in Bilirubin, Direct Bilirubin, Indirect Bilirubin Levels | Direct bilirubin; Day 43; n= 15, 20, 18, 21, 21 | 0.3 µmol/L | Standard Deviation 1.03 |
| Dapro 15 mg | Change From Baseline in Bilirubin, Direct Bilirubin, Indirect Bilirubin Levels | Bilirubin; Day 15; n= 17, 20, 18, 22, 20 | 0.8 µmol/L | Standard Deviation 2.07 |
| Dapro 15 mg | Change From Baseline in Bilirubin, Direct Bilirubin, Indirect Bilirubin Levels | Bilirubin; Day 29; n= 17, 19, 18, 19, 17 | 1.0 µmol/L | Standard Deviation 1.41 |
| Dapro 15 mg | Change From Baseline in Bilirubin, Direct Bilirubin, Indirect Bilirubin Levels | Bilirubin; Day 43; n= 15, 20, 18, 21, 21 | 0.6 µmol/L | Standard Deviation 2.04 |
| Dapro 15 mg | Change From Baseline in Bilirubin, Direct Bilirubin, Indirect Bilirubin Levels | Direct bilirubin; Day 15; n= 17, 20, 18, 22, 20 | 0.6 µmol/L | Standard Deviation 0.92 |
| Dapro 15 mg | Change From Baseline in Bilirubin, Direct Bilirubin, Indirect Bilirubin Levels | Direct bilirubin; Day 29; n= 17, 19, 18, 19, 17 | 0.7 µmol/L | Standard Deviation 0.97 |
| Dapro 15 mg | Change From Baseline in Bilirubin, Direct Bilirubin, Indirect Bilirubin Levels | Indirect bilirubin; Day 15; n= 17, 20, 18, 22, 20 | 0.2 µmol/L | Standard Deviation 1.8 |
| Dapro 15 mg | Change From Baseline in Bilirubin, Direct Bilirubin, Indirect Bilirubin Levels | Indirect bilirubin; Day 29; n= 17, 19, 18, 19, 17 | 0.3 µmol/L | Standard Deviation 1.71 |
| Dapro 15 mg | Change From Baseline in Bilirubin, Direct Bilirubin, Indirect Bilirubin Levels | Indirect bilirubin; Day 43; n= 15, 20, 18, 21, 21 | 0.2 µmol/L | Standard Deviation 1.66 |
| Dapro 25 mg | Change From Baseline in Bilirubin, Direct Bilirubin, Indirect Bilirubin Levels | Direct bilirubin; Day 15; n= 17, 20, 18, 22, 20 | -0.1 µmol/L | Standard Deviation 0.97 |
| Dapro 25 mg | Change From Baseline in Bilirubin, Direct Bilirubin, Indirect Bilirubin Levels | Direct bilirubin; Day 43; n= 15, 20, 18, 21, 21 | -0.2 µmol/L | Standard Deviation 1.08 |
| Dapro 25 mg | Change From Baseline in Bilirubin, Direct Bilirubin, Indirect Bilirubin Levels | Bilirubin; Day 43; n= 15, 20, 18, 21, 21 | 0.1 µmol/L | Standard Deviation 1.34 |
| Dapro 25 mg | Change From Baseline in Bilirubin, Direct Bilirubin, Indirect Bilirubin Levels | Indirect bilirubin; Day 15; n= 17, 20, 18, 22, 20 | 0.1 µmol/L | Standard Deviation 1.44 |
| Dapro 25 mg | Change From Baseline in Bilirubin, Direct Bilirubin, Indirect Bilirubin Levels | Bilirubin; Day 29; n= 17, 19, 18, 19, 17 | 0.1 µmol/L | Standard Deviation 1.56 |
| Dapro 25 mg | Change From Baseline in Bilirubin, Direct Bilirubin, Indirect Bilirubin Levels | Indirect bilirubin; Day 43; n= 15, 20, 18, 21, 21 | 0.3 µmol/L | Standard Deviation 1.82 |
| Dapro 25 mg | Change From Baseline in Bilirubin, Direct Bilirubin, Indirect Bilirubin Levels | Indirect bilirubin; Day 29; n= 17, 19, 18, 19, 17 | 0.2 µmol/L | Standard Deviation 1.62 |
| Dapro 25 mg | Change From Baseline in Bilirubin, Direct Bilirubin, Indirect Bilirubin Levels | Bilirubin; Day 15; n= 17, 20, 18, 22, 20 | 0.0 µmol/L | Standard Deviation 1.38 |
| Dapro 25 mg | Change From Baseline in Bilirubin, Direct Bilirubin, Indirect Bilirubin Levels | Direct bilirubin; Day 29; n= 17, 19, 18, 19, 17 | -0.1 µmol/L | Standard Deviation 1.05 |
| Dapro 30 mg | Change From Baseline in Bilirubin, Direct Bilirubin, Indirect Bilirubin Levels | Bilirubin; Day 15; n= 17, 20, 18, 22, 20 | 0.5 µmol/L | Standard Deviation 1.93 |
| Dapro 30 mg | Change From Baseline in Bilirubin, Direct Bilirubin, Indirect Bilirubin Levels | Direct bilirubin; Day 15; n= 17, 20, 18, 22, 20 | 0.2 µmol/L | Standard Deviation 1.11 |
| Dapro 30 mg | Change From Baseline in Bilirubin, Direct Bilirubin, Indirect Bilirubin Levels | Direct bilirubin; Day 43; n= 15, 20, 18, 21, 21 | -0.1 µmol/L | Standard Deviation 1.34 |
| Dapro 30 mg | Change From Baseline in Bilirubin, Direct Bilirubin, Indirect Bilirubin Levels | Bilirubin; Day 43; n= 15, 20, 18, 21, 21 | 0.4 µmol/L | Standard Deviation 1.36 |
| Dapro 30 mg | Change From Baseline in Bilirubin, Direct Bilirubin, Indirect Bilirubin Levels | Direct bilirubin; Day 29; n= 17, 19, 18, 19, 17 | -0.1 µmol/L | Standard Deviation 1.5 |
| Dapro 30 mg | Change From Baseline in Bilirubin, Direct Bilirubin, Indirect Bilirubin Levels | Indirect bilirubin; Day 43; n= 15, 20, 18, 21, 21 | 0.5 µmol/L | Standard Deviation 1.4 |
| Dapro 30 mg | Change From Baseline in Bilirubin, Direct Bilirubin, Indirect Bilirubin Levels | Indirect bilirubin; Day 29; n= 17, 19, 18, 19, 17 | 0.4 µmol/L | Standard Deviation 1.46 |
| Dapro 30 mg | Change From Baseline in Bilirubin, Direct Bilirubin, Indirect Bilirubin Levels | Indirect bilirubin; Day 15; n= 17, 20, 18, 22, 20 | 0.3 µmol/L | Standard Deviation 1.75 |
| Dapro 30 mg | Change From Baseline in Bilirubin, Direct Bilirubin, Indirect Bilirubin Levels | Bilirubin; Day 29; n= 17, 19, 18, 19, 17 | 0.2 µmol/L | Standard Deviation 0.97 |
Secondary
Change From Baseline in ECG Mean Heart Rate
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
Population: Safety Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in ECG Mean Heart Rate | -2.0 Beats per minute | Standard Deviation 8.66 |
| Dapro 10 mg | Change From Baseline in ECG Mean Heart Rate | 0.5 Beats per minute | Standard Deviation 10.53 |
| Dapro 15 mg | Change From Baseline in ECG Mean Heart Rate | 1.1 Beats per minute | Standard Deviation 7.4 |
| Dapro 25 mg | Change From Baseline in ECG Mean Heart Rate | 2.2 Beats per minute | Standard Deviation 7.51 |
| Dapro 30 mg | Change From Baseline in ECG Mean Heart Rate | 0.9 Beats per minute | Standard Deviation 7.09 |
Secondary
Change From Baseline in ECG Parameters Including PR Interval, QRS Duration, QT Interval and QTcB
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in ECG Parameters Including PR Interval, QRS Duration, QT Interval and QTcB | PR interval; n= 17, 18, 18, 17, 16 | 7.8 Milliseconds (msec) | Standard Deviation 16.86 |
| Placebo | Change From Baseline in ECG Parameters Including PR Interval, QRS Duration, QT Interval and QTcB | QRS duration; n= 17, 19, 18, 19, 17 | -1.4 Milliseconds (msec) | Standard Deviation 14.05 |
| Placebo | Change From Baseline in ECG Parameters Including PR Interval, QRS Duration, QT Interval and QTcB | QT interval; n= 17, 19, 18, 19, 17 | 10.5 Milliseconds (msec) | Standard Deviation 27.16 |
| Placebo | Change From Baseline in ECG Parameters Including PR Interval, QRS Duration, QT Interval and QTcB | QTcB; n= 17, 19, 18, 19, 17 | 0.0 Milliseconds (msec) | Standard Deviation 30.84 |
| Dapro 10 mg | Change From Baseline in ECG Parameters Including PR Interval, QRS Duration, QT Interval and QTcB | PR interval; n= 17, 18, 18, 17, 16 | 7.3 Milliseconds (msec) | Standard Deviation 12.37 |
| Dapro 10 mg | Change From Baseline in ECG Parameters Including PR Interval, QRS Duration, QT Interval and QTcB | QTcB; n= 17, 19, 18, 19, 17 | 5.6 Milliseconds (msec) | Standard Deviation 17.4 |
| Dapro 10 mg | Change From Baseline in ECG Parameters Including PR Interval, QRS Duration, QT Interval and QTcB | QRS duration; n= 17, 19, 18, 19, 17 | -5.7 Milliseconds (msec) | Standard Deviation 13.36 |
| Dapro 10 mg | Change From Baseline in ECG Parameters Including PR Interval, QRS Duration, QT Interval and QTcB | QT interval; n= 17, 19, 18, 19, 17 | 0.7 Milliseconds (msec) | Standard Deviation 31.11 |
| Dapro 15 mg | Change From Baseline in ECG Parameters Including PR Interval, QRS Duration, QT Interval and QTcB | QTcB; n= 17, 19, 18, 19, 17 | -3.7 Milliseconds (msec) | Standard Deviation 44.86 |
| Dapro 15 mg | Change From Baseline in ECG Parameters Including PR Interval, QRS Duration, QT Interval and QTcB | QRS duration; n= 17, 19, 18, 19, 17 | -4.7 Milliseconds (msec) | Standard Deviation 47.01 |
| Dapro 15 mg | Change From Baseline in ECG Parameters Including PR Interval, QRS Duration, QT Interval and QTcB | QT interval; n= 17, 19, 18, 19, 17 | -19.2 Milliseconds (msec) | Standard Deviation 62.37 |
| Dapro 15 mg | Change From Baseline in ECG Parameters Including PR Interval, QRS Duration, QT Interval and QTcB | PR interval; n= 17, 18, 18, 17, 16 | -3.3 Milliseconds (msec) | Standard Deviation 23.04 |
| Dapro 25 mg | Change From Baseline in ECG Parameters Including PR Interval, QRS Duration, QT Interval and QTcB | PR interval; n= 17, 18, 18, 17, 16 | 2.1 Milliseconds (msec) | Standard Deviation 27.13 |
| Dapro 25 mg | Change From Baseline in ECG Parameters Including PR Interval, QRS Duration, QT Interval and QTcB | QRS duration; n= 17, 19, 18, 19, 17 | 1.7 Milliseconds (msec) | Standard Deviation 14.33 |
| Dapro 25 mg | Change From Baseline in ECG Parameters Including PR Interval, QRS Duration, QT Interval and QTcB | QTcB; n= 17, 19, 18, 19, 17 | 1.1 Milliseconds (msec) | Standard Deviation 20.84 |
| Dapro 25 mg | Change From Baseline in ECG Parameters Including PR Interval, QRS Duration, QT Interval and QTcB | QT interval; n= 17, 19, 18, 19, 17 | -1.4 Milliseconds (msec) | Standard Deviation 17.72 |
| Dapro 30 mg | Change From Baseline in ECG Parameters Including PR Interval, QRS Duration, QT Interval and QTcB | QTcB; n= 17, 19, 18, 19, 17 | -5.7 Milliseconds (msec) | Standard Deviation 31.65 |
| Dapro 30 mg | Change From Baseline in ECG Parameters Including PR Interval, QRS Duration, QT Interval and QTcB | QT interval; n= 17, 19, 18, 19, 17 | -8.2 Milliseconds (msec) | Standard Deviation 33.24 |
| Dapro 30 mg | Change From Baseline in ECG Parameters Including PR Interval, QRS Duration, QT Interval and QTcB | QRS duration; n= 17, 19, 18, 19, 17 | 2.5 Milliseconds (msec) | Standard Deviation 8.97 |
| Dapro 30 mg | Change From Baseline in ECG Parameters Including PR Interval, QRS Duration, QT Interval and QTcB | PR interval; n= 17, 18, 18, 17, 16 | -11.5 Milliseconds (msec) | Standard Deviation 24.77 |
Secondary
Change From Baseline in Erythrocyte Distribution Width Levels
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Erythrocyte Distribution Width Levels | Day 15; n= 17, 19, 17, 21, 21 | -0.18 Percentage of width | Standard Deviation 1.025 |
| Placebo | Change From Baseline in Erythrocyte Distribution Width Levels | Day 43; n= 16, 20, 19, 21, 20 | 0.18 Percentage of width | Standard Deviation 1.329 |
| Placebo | Change From Baseline in Erythrocyte Distribution Width Levels | Day 29; n= 16, 19, 17, 18, 17 | -0.31 Percentage of width | Standard Deviation 1.019 |
| Dapro 10 mg | Change From Baseline in Erythrocyte Distribution Width Levels | Day 29; n= 16, 19, 17, 18, 17 | -0.64 Percentage of width | Standard Deviation 1.332 |
| Dapro 10 mg | Change From Baseline in Erythrocyte Distribution Width Levels | Day 15; n= 17, 19, 17, 21, 21 | -0.48 Percentage of width | Standard Deviation 1.276 |
| Dapro 10 mg | Change From Baseline in Erythrocyte Distribution Width Levels | Day 43; n= 16, 20, 19, 21, 20 | -0.74 Percentage of width | Standard Deviation 1.728 |
| Dapro 15 mg | Change From Baseline in Erythrocyte Distribution Width Levels | Day 29; n= 16, 19, 17, 18, 17 | -0.23 Percentage of width | Standard Deviation 1.021 |
| Dapro 15 mg | Change From Baseline in Erythrocyte Distribution Width Levels | Day 15; n= 17, 19, 17, 21, 21 | -0.09 Percentage of width | Standard Deviation 1.047 |
| Dapro 15 mg | Change From Baseline in Erythrocyte Distribution Width Levels | Day 43; n= 16, 20, 19, 21, 20 | -0.50 Percentage of width | Standard Deviation 1.094 |
| Dapro 25 mg | Change From Baseline in Erythrocyte Distribution Width Levels | Day 15; n= 17, 19, 17, 21, 21 | 0.54 Percentage of width | Standard Deviation 1.162 |
| Dapro 25 mg | Change From Baseline in Erythrocyte Distribution Width Levels | Day 43; n= 16, 20, 19, 21, 20 | 0.23 Percentage of width | Standard Deviation 1.41 |
| Dapro 25 mg | Change From Baseline in Erythrocyte Distribution Width Levels | Day 29; n= 16, 19, 17, 18, 17 | 0.58 Percentage of width | Standard Deviation 1.202 |
| Dapro 30 mg | Change From Baseline in Erythrocyte Distribution Width Levels | Day 29; n= 16, 19, 17, 18, 17 | 0.40 Percentage of width | Standard Deviation 1.342 |
| Dapro 30 mg | Change From Baseline in Erythrocyte Distribution Width Levels | Day 15; n= 17, 19, 17, 21, 21 | 1.06 Percentage of width | Standard Deviation 1.337 |
| Dapro 30 mg | Change From Baseline in Erythrocyte Distribution Width Levels | Day 43; n= 16, 20, 19, 21, 20 | -0.22 Percentage of width | Standard Deviation 1.165 |
Secondary
Change From Baseline in Hematocrit Levels
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
Population: ITT Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Hematocrit Levels | -0.0218 Proportion of red blood cells in blood | Standard Deviation 0.02469 |
| Dapro 10 mg | Change From Baseline in Hematocrit Levels | -0.0127 Proportion of red blood cells in blood | Standard Deviation 0.05396 |
| Dapro 15 mg | Change From Baseline in Hematocrit Levels | -0.0149 Proportion of red blood cells in blood | Standard Deviation 0.05379 |
| Dapro 25 mg | Change From Baseline in Hematocrit Levels | 0.0150 Proportion of red blood cells in blood | Standard Deviation 0.04511 |
| Dapro 30 mg | Change From Baseline in Hematocrit Levels | 0.0215 Proportion of red blood cells in blood | Standard Deviation 0.03852 |
Secondary
Change From Baseline in Leukocytes, Neutrophils, Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets Levels
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Leukocytes, Neutrophils, Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets Levels | Basophils; Day 43; n= 16, 20, 19, 19, 19 | 0.006 10^12 cells/L | Standard Deviation 0.0268 |
| Placebo | Change From Baseline in Leukocytes, Neutrophils, Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets Levels | Basophils; Day 29; n= 16, 18, 17, 17, 15 | 0.013 10^12 cells/L | Standard Deviation 0.051 |
| Placebo | Change From Baseline in Leukocytes, Neutrophils, Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets Levels | Neutrophils; Day 29; n= 16, 18, 17, 17, 15 | 0.237 10^12 cells/L | Standard Deviation 1.6283 |
| Placebo | Change From Baseline in Leukocytes, Neutrophils, Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets Levels | Platelet; Day 15; n= 17, 18, 17, 20, 21 | -14.2 10^12 cells/L | Standard Deviation 26.24 |
| Placebo | Change From Baseline in Leukocytes, Neutrophils, Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets Levels | Basophils; Day 15; n= 17, 19, 17, 21, 21 | 0.005 10^12 cells/L | Standard Deviation 0.0302 |
| Placebo | Change From Baseline in Leukocytes, Neutrophils, Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets Levels | Neutrophils; Day 43; n= 16, 20, 19, 19, 19 | 0.423 10^12 cells/L | Standard Deviation 1.0535 |
| Placebo | Change From Baseline in Leukocytes, Neutrophils, Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets Levels | Monocytes; Day 43; n= 16, 20, 19, 19, 19 | 0.033 10^12 cells/L | Standard Deviation 0.1631 |
| Placebo | Change From Baseline in Leukocytes, Neutrophils, Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets Levels | Monocytes; Day 29; n= 16, 18, 17, 17, 15 | 0.027 10^12 cells/L | Standard Deviation 0.1553 |
| Placebo | Change From Baseline in Leukocytes, Neutrophils, Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets Levels | Leukocytes; Day 29; n= 16, 19, 17, 18, 17 | 0.49 10^12 cells/L | Standard Deviation 1.849 |
| Placebo | Change From Baseline in Leukocytes, Neutrophils, Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets Levels | Platelet; Day 29; n= 16, 18, 17, 17, 17 | -17.1 10^12 cells/L | Standard Deviation 40.58 |
| Placebo | Change From Baseline in Leukocytes, Neutrophils, Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets Levels | Monocytes; Day 15; n= 17, 19, 17, 21, 21 | -0.005 10^12 cells/L | Standard Deviation 0.1518 |
| Placebo | Change From Baseline in Leukocytes, Neutrophils, Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets Levels | Lymphocytes; Day 43; n= 16, 20, 19, 19, 19 | 0.018 10^12 cells/L | Standard Deviation 0.3427 |
| Placebo | Change From Baseline in Leukocytes, Neutrophils, Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets Levels | Lymphocytes; Day 29; n= 16, 18, 17, 17, 15 | 0.194 10^12 cells/L | Standard Deviation 0.6605 |
| Placebo | Change From Baseline in Leukocytes, Neutrophils, Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets Levels | Leukocytes; Day 43; n= 16, 20, 19, 20, 19 | 0.54 10^12 cells/L | Standard Deviation 1.041 |
| Placebo | Change From Baseline in Leukocytes, Neutrophils, Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets Levels | Leukocytes; Day 15; n= 17, 19, 17, 21, 21 | 0.47 10^12 cells/L | Standard Deviation 1.271 |
| Placebo | Change From Baseline in Leukocytes, Neutrophils, Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets Levels | Lymphocytes; Day 15; n= 17, 19, 17, 21, 21 | 0.082 10^12 cells/L | Standard Deviation 0.4256 |
| Placebo | Change From Baseline in Leukocytes, Neutrophils, Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets Levels | Eosinophils; Day 43; n= 16, 20, 19, 19, 19 | 0.061 10^12 cells/L | Standard Deviation 0.1193 |
| Placebo | Change From Baseline in Leukocytes, Neutrophils, Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets Levels | Eosinophils; Day 29; n= 16, 18, 17, 17, 15 | 0.020 10^12 cells/L | Standard Deviation 0.0859 |
| Placebo | Change From Baseline in Leukocytes, Neutrophils, Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets Levels | Neutrophils; Day 15; n= 17, 19, 17, 21, 21 | 0.391 10^12 cells/L | Standard Deviation 1.2323 |
| Placebo | Change From Baseline in Leukocytes, Neutrophils, Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets Levels | Platelet; Day 43; n= 15, 19, 19, 21, 20 | -4.9 10^12 cells/L | Standard Deviation 37.3 |
| Placebo | Change From Baseline in Leukocytes, Neutrophils, Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets Levels | Eosinophils; Day 15; n= 17, 19, 17, 21, 21 | 0.009 10^12 cells/L | Standard Deviation 0.0698 |
| Dapro 10 mg | Change From Baseline in Leukocytes, Neutrophils, Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets Levels | Basophils; Day 29; n= 16, 18, 17, 17, 15 | 0.006 10^12 cells/L | Standard Deviation 0.0195 |
| Dapro 10 mg | Change From Baseline in Leukocytes, Neutrophils, Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets Levels | Leukocytes; Day 15; n= 17, 19, 17, 21, 21 | -0.21 10^12 cells/L | Standard Deviation 1.051 |
| Dapro 10 mg | Change From Baseline in Leukocytes, Neutrophils, Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets Levels | Leukocytes; Day 29; n= 16, 19, 17, 18, 17 | 0.40 10^12 cells/L | Standard Deviation 1.784 |
| Dapro 10 mg | Change From Baseline in Leukocytes, Neutrophils, Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets Levels | Leukocytes; Day 43; n= 16, 20, 19, 20, 19 | 1.08 10^12 cells/L | Standard Deviation 1.662 |
| Dapro 10 mg | Change From Baseline in Leukocytes, Neutrophils, Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets Levels | Neutrophils; Day 15; n= 17, 19, 17, 21, 21 | -0.146 10^12 cells/L | Standard Deviation 0.9163 |
| Dapro 10 mg | Change From Baseline in Leukocytes, Neutrophils, Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets Levels | Neutrophils; Day 29; n= 16, 18, 17, 17, 15 | 0.469 10^12 cells/L | Standard Deviation 1.5717 |
| Dapro 10 mg | Change From Baseline in Leukocytes, Neutrophils, Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets Levels | Neutrophils; Day 43; n= 16, 20, 19, 19, 19 | 0.904 10^12 cells/L | Standard Deviation 1.3737 |
| Dapro 10 mg | Change From Baseline in Leukocytes, Neutrophils, Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets Levels | Basophils; Day 15; n= 17, 19, 17, 21, 21 | 0.009 10^12 cells/L | Standard Deviation 0.02 |
| Dapro 10 mg | Change From Baseline in Leukocytes, Neutrophils, Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets Levels | Basophils; Day 43; n= 16, 20, 19, 19, 19 | 0.001 10^12 cells/L | Standard Deviation 0.0148 |
| Dapro 10 mg | Change From Baseline in Leukocytes, Neutrophils, Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets Levels | Eosinophils; Day 15; n= 17, 19, 17, 21, 21 | -0.017 10^12 cells/L | Standard Deviation 0.1313 |
| Dapro 10 mg | Change From Baseline in Leukocytes, Neutrophils, Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets Levels | Eosinophils; Day 29; n= 16, 18, 17, 17, 15 | -0.002 10^12 cells/L | Standard Deviation 0.1226 |
| Dapro 10 mg | Change From Baseline in Leukocytes, Neutrophils, Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets Levels | Eosinophils; Day 43; n= 16, 20, 19, 19, 19 | 0.030 10^12 cells/L | Standard Deviation 0.1439 |
| Dapro 10 mg | Change From Baseline in Leukocytes, Neutrophils, Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets Levels | Lymphocytes; Day 15; n= 17, 19, 17, 21, 21 | -0.019 10^12 cells/L | Standard Deviation 0.3163 |
| Dapro 10 mg | Change From Baseline in Leukocytes, Neutrophils, Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets Levels | Lymphocytes; Day 29; n= 16, 18, 17, 17, 15 | 0.026 10^12 cells/L | Standard Deviation 0.413 |
| Dapro 10 mg | Change From Baseline in Leukocytes, Neutrophils, Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets Levels | Lymphocytes; Day 43; n= 16, 20, 19, 19, 19 | 0.061 10^12 cells/L | Standard Deviation 0.3332 |
| Dapro 10 mg | Change From Baseline in Leukocytes, Neutrophils, Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets Levels | Monocytes; Day 15; n= 17, 19, 17, 21, 21 | -0.042 10^12 cells/L | Standard Deviation 0.1504 |
| Dapro 10 mg | Change From Baseline in Leukocytes, Neutrophils, Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets Levels | Monocytes; Day 29; n= 16, 18, 17, 17, 15 | 0.053 10^12 cells/L | Standard Deviation 0.1483 |
| Dapro 10 mg | Change From Baseline in Leukocytes, Neutrophils, Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets Levels | Monocytes; Day 43; n= 16, 20, 19, 19, 19 | 0.065 10^12 cells/L | Standard Deviation 0.1629 |
| Dapro 10 mg | Change From Baseline in Leukocytes, Neutrophils, Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets Levels | Platelet; Day 15; n= 17, 18, 17, 20, 21 | -16.2 10^12 cells/L | Standard Deviation 27.46 |
| Dapro 10 mg | Change From Baseline in Leukocytes, Neutrophils, Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets Levels | Platelet; Day 29; n= 16, 18, 17, 17, 17 | -12.8 10^12 cells/L | Standard Deviation 36.55 |
| Dapro 10 mg | Change From Baseline in Leukocytes, Neutrophils, Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets Levels | Platelet; Day 43; n= 15, 19, 19, 21, 20 | 4.4 10^12 cells/L | Standard Deviation 50.34 |
| Dapro 15 mg | Change From Baseline in Leukocytes, Neutrophils, Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets Levels | Monocytes; Day 29; n= 16, 18, 17, 17, 15 | -0.031 10^12 cells/L | Standard Deviation 0.2194 |
| Dapro 15 mg | Change From Baseline in Leukocytes, Neutrophils, Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets Levels | Lymphocytes; Day 15; n= 17, 19, 17, 21, 21 | 0.106 10^12 cells/L | Standard Deviation 0.4617 |
| Dapro 15 mg | Change From Baseline in Leukocytes, Neutrophils, Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets Levels | Basophils; Day 43; n= 16, 20, 19, 19, 19 | -0.004 10^12 cells/L | Standard Deviation 0.0203 |
| Dapro 15 mg | Change From Baseline in Leukocytes, Neutrophils, Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets Levels | Monocytes; Day 15; n= 17, 19, 17, 21, 21 | -0.016 10^12 cells/L | Standard Deviation 0.2285 |
| Dapro 15 mg | Change From Baseline in Leukocytes, Neutrophils, Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets Levels | Leukocytes; Day 29; n= 16, 19, 17, 18, 17 | 0.00 10^12 cells/L | Standard Deviation 1.084 |
| Dapro 15 mg | Change From Baseline in Leukocytes, Neutrophils, Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets Levels | Platelet; Day 43; n= 15, 19, 19, 21, 20 | -10.4 10^12 cells/L | Standard Deviation 35.12 |
| Dapro 15 mg | Change From Baseline in Leukocytes, Neutrophils, Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets Levels | Lymphocytes; Day 29; n= 16, 18, 17, 17, 15 | 0.019 10^12 cells/L | Standard Deviation 0.4421 |
| Dapro 15 mg | Change From Baseline in Leukocytes, Neutrophils, Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets Levels | Basophils; Day 15; n= 17, 19, 17, 21, 21 | -0.002 10^12 cells/L | Standard Deviation 0.021 |
| Dapro 15 mg | Change From Baseline in Leukocytes, Neutrophils, Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets Levels | Lymphocytes; Day 43; n= 16, 20, 19, 19, 19 | 0.007 10^12 cells/L | Standard Deviation 0.4824 |
| Dapro 15 mg | Change From Baseline in Leukocytes, Neutrophils, Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets Levels | Leukocytes; Day 15; n= 17, 19, 17, 21, 21 | 0.40 10^12 cells/L | Standard Deviation 1.116 |
| Dapro 15 mg | Change From Baseline in Leukocytes, Neutrophils, Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets Levels | Platelet; Day 29; n= 16, 18, 17, 17, 17 | -18.1 10^12 cells/L | Standard Deviation 29.63 |
| Dapro 15 mg | Change From Baseline in Leukocytes, Neutrophils, Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets Levels | Basophils; Day 29; n= 16, 18, 17, 17, 15 | -0.004 10^12 cells/L | Standard Deviation 0.0187 |
| Dapro 15 mg | Change From Baseline in Leukocytes, Neutrophils, Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets Levels | Eosinophils; Day 29; n= 16, 18, 17, 17, 15 | -0.006 10^12 cells/L | Standard Deviation 0.1129 |
| Dapro 15 mg | Change From Baseline in Leukocytes, Neutrophils, Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets Levels | Neutrophils; Day 15; n= 17, 19, 17, 21, 21 | 0.280 10^12 cells/L | Standard Deviation 1.0681 |
| Dapro 15 mg | Change From Baseline in Leukocytes, Neutrophils, Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets Levels | Neutrophils; Day 29; n= 16, 18, 17, 17, 15 | -0.021 10^12 cells/L | Standard Deviation 1.0157 |
| Dapro 15 mg | Change From Baseline in Leukocytes, Neutrophils, Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets Levels | Platelet; Day 15; n= 17, 18, 17, 20, 21 | -3.2 10^12 cells/L | Standard Deviation 38.13 |
| Dapro 15 mg | Change From Baseline in Leukocytes, Neutrophils, Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets Levels | Neutrophils; Day 43; n= 16, 20, 19, 19, 19 | 0.112 10^12 cells/L | Standard Deviation 1.0449 |
| Dapro 15 mg | Change From Baseline in Leukocytes, Neutrophils, Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets Levels | Eosinophils; Day 43; n= 16, 20, 19, 19, 19 | 0.051 10^12 cells/L | Standard Deviation 0.1647 |
| Dapro 15 mg | Change From Baseline in Leukocytes, Neutrophils, Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets Levels | Eosinophils; Day 15; n= 17, 19, 17, 21, 21 | -0.006 10^12 cells/L | Standard Deviation 0.1345 |
| Dapro 15 mg | Change From Baseline in Leukocytes, Neutrophils, Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets Levels | Monocytes; Day 43; n= 16, 20, 19, 19, 19 | 0.026 10^12 cells/L | Standard Deviation 0.2652 |
| Dapro 15 mg | Change From Baseline in Leukocytes, Neutrophils, Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets Levels | Leukocytes; Day 43; n= 16, 20, 19, 20, 19 | 0.23 10^12 cells/L | Standard Deviation 1.101 |
| Dapro 25 mg | Change From Baseline in Leukocytes, Neutrophils, Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets Levels | Neutrophils; Day 15; n= 17, 19, 17, 21, 21 | 0.259 10^12 cells/L | Standard Deviation 1.3874 |
| Dapro 25 mg | Change From Baseline in Leukocytes, Neutrophils, Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets Levels | Platelet; Day 43; n= 15, 19, 19, 21, 20 | -1.6 10^12 cells/L | Standard Deviation 30.95 |
| Dapro 25 mg | Change From Baseline in Leukocytes, Neutrophils, Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets Levels | Basophils; Day 43; n= 16, 20, 19, 19, 19 | -0.001 10^12 cells/L | Standard Deviation 0.0228 |
| Dapro 25 mg | Change From Baseline in Leukocytes, Neutrophils, Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets Levels | Eosinophils; Day 15; n= 17, 19, 17, 21, 21 | -0.006 10^12 cells/L | Standard Deviation 0.1183 |
| Dapro 25 mg | Change From Baseline in Leukocytes, Neutrophils, Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets Levels | Platelet; Day 15; n= 17, 18, 17, 20, 21 | -3.3 10^12 cells/L | Standard Deviation 27.78 |
| Dapro 25 mg | Change From Baseline in Leukocytes, Neutrophils, Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets Levels | Eosinophils; Day 29; n= 16, 18, 17, 17, 15 | 0.025 10^12 cells/L | Standard Deviation 0.099 |
| Dapro 25 mg | Change From Baseline in Leukocytes, Neutrophils, Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets Levels | Leukocytes; Day 43; n= 16, 20, 19, 20, 19 | 0.21 10^12 cells/L | Standard Deviation 2.615 |
| Dapro 25 mg | Change From Baseline in Leukocytes, Neutrophils, Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets Levels | Eosinophils; Day 43; n= 16, 20, 19, 19, 19 | 0.021 10^12 cells/L | Standard Deviation 0.0984 |
| Dapro 25 mg | Change From Baseline in Leukocytes, Neutrophils, Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets Levels | Lymphocytes; Day 15; n= 17, 19, 17, 21, 21 | -0.208 10^12 cells/L | Standard Deviation 0.5095 |
| Dapro 25 mg | Change From Baseline in Leukocytes, Neutrophils, Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets Levels | Lymphocytes; Day 29; n= 16, 18, 17, 17, 15 | -0.074 10^12 cells/L | Standard Deviation 0.7018 |
| Dapro 25 mg | Change From Baseline in Leukocytes, Neutrophils, Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets Levels | Leukocytes; Day 29; n= 16, 19, 17, 18, 17 | -0.14 10^12 cells/L | Standard Deviation 1.701 |
| Dapro 25 mg | Change From Baseline in Leukocytes, Neutrophils, Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets Levels | Lymphocytes; Day 43; n= 16, 20, 19, 19, 19 | -0.064 10^12 cells/L | Standard Deviation 0.4759 |
| Dapro 25 mg | Change From Baseline in Leukocytes, Neutrophils, Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets Levels | Platelet; Day 29; n= 16, 18, 17, 17, 17 | 1.3 10^12 cells/L | Standard Deviation 35.58 |
| Dapro 25 mg | Change From Baseline in Leukocytes, Neutrophils, Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets Levels | Monocytes; Day 15; n= 17, 19, 17, 21, 21 | -0.068 10^12 cells/L | Standard Deviation 0.1895 |
| Dapro 25 mg | Change From Baseline in Leukocytes, Neutrophils, Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets Levels | Monocytes; Day 29; n= 16, 18, 17, 17, 15 | 0.077 10^12 cells/L | Standard Deviation 0.2532 |
| Dapro 25 mg | Change From Baseline in Leukocytes, Neutrophils, Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets Levels | Leukocytes; Day 15; n= 17, 19, 17, 21, 21 | -0.03 10^12 cells/L | Standard Deviation 1.476 |
| Dapro 25 mg | Change From Baseline in Leukocytes, Neutrophils, Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets Levels | Monocytes; Day 43; n= 16, 20, 19, 19, 19 | -0.021 10^12 cells/L | Standard Deviation 0.1855 |
| Dapro 25 mg | Change From Baseline in Leukocytes, Neutrophils, Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets Levels | Neutrophils; Day 29; n= 16, 18, 17, 17, 15 | -0.009 10^12 cells/L | Standard Deviation 1.8718 |
| Dapro 25 mg | Change From Baseline in Leukocytes, Neutrophils, Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets Levels | Neutrophils; Day 43; n= 16, 20, 19, 19, 19 | 0.504 10^12 cells/L | Standard Deviation 2.311 |
| Dapro 25 mg | Change From Baseline in Leukocytes, Neutrophils, Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets Levels | Basophils; Day 15; n= 17, 19, 17, 21, 21 | -0.002 10^12 cells/L | Standard Deviation 0.0383 |
| Dapro 25 mg | Change From Baseline in Leukocytes, Neutrophils, Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets Levels | Basophils; Day 29; n= 16, 18, 17, 17, 15 | 0.000 10^12 cells/L | Standard Deviation 0.0242 |
| Dapro 30 mg | Change From Baseline in Leukocytes, Neutrophils, Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets Levels | Platelet; Day 43; n= 15, 19, 19, 21, 20 | -7.1 10^12 cells/L | Standard Deviation 31.95 |
| Dapro 30 mg | Change From Baseline in Leukocytes, Neutrophils, Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets Levels | Eosinophils; Day 15; n= 17, 19, 17, 21, 21 | -0.053 10^12 cells/L | Standard Deviation 0.1478 |
| Dapro 30 mg | Change From Baseline in Leukocytes, Neutrophils, Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets Levels | Basophils; Day 29; n= 16, 18, 17, 17, 15 | 0.012 10^12 cells/L | Standard Deviation 0.0328 |
| Dapro 30 mg | Change From Baseline in Leukocytes, Neutrophils, Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets Levels | Monocytes; Day 29; n= 16, 18, 17, 17, 15 | 0.015 10^12 cells/L | Standard Deviation 0.1878 |
| Dapro 30 mg | Change From Baseline in Leukocytes, Neutrophils, Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets Levels | Eosinophils; Day 43; n= 16, 20, 19, 19, 19 | -0.024 10^12 cells/L | Standard Deviation 0.1876 |
| Dapro 30 mg | Change From Baseline in Leukocytes, Neutrophils, Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets Levels | Basophils; Day 15; n= 17, 19, 17, 21, 21 | 0.007 10^12 cells/L | Standard Deviation 0.0102 |
| Dapro 30 mg | Change From Baseline in Leukocytes, Neutrophils, Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets Levels | Neutrophils; Day 29; n= 16, 18, 17, 17, 15 | 0.273 10^12 cells/L | Standard Deviation 1.5729 |
| Dapro 30 mg | Change From Baseline in Leukocytes, Neutrophils, Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets Levels | Neutrophils; Day 15; n= 17, 19, 17, 21, 21 | 0.344 10^12 cells/L | Standard Deviation 1.2469 |
| Dapro 30 mg | Change From Baseline in Leukocytes, Neutrophils, Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets Levels | Monocytes; Day 43; n= 16, 20, 19, 19, 19 | 0.023 10^12 cells/L | Standard Deviation 0.1249 |
| Dapro 30 mg | Change From Baseline in Leukocytes, Neutrophils, Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets Levels | Platelet; Day 15; n= 17, 18, 17, 20, 21 | -10.8 10^12 cells/L | Standard Deviation 31.95 |
| Dapro 30 mg | Change From Baseline in Leukocytes, Neutrophils, Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets Levels | Basophils; Day 43; n= 16, 20, 19, 19, 19 | 0.007 10^12 cells/L | Standard Deviation 0.0192 |
| Dapro 30 mg | Change From Baseline in Leukocytes, Neutrophils, Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets Levels | Lymphocytes; Day 29; n= 16, 18, 17, 17, 15 | -0.154 10^12 cells/L | Standard Deviation 0.3058 |
| Dapro 30 mg | Change From Baseline in Leukocytes, Neutrophils, Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets Levels | Neutrophils; Day 43; n= 16, 20, 19, 19, 19 | 0.691 10^12 cells/L | Standard Deviation 1.5221 |
| Dapro 30 mg | Change From Baseline in Leukocytes, Neutrophils, Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets Levels | Lymphocytes; Day 43; n= 16, 20, 19, 19, 19 | -0.041 10^12 cells/L | Standard Deviation 0.2801 |
| Dapro 30 mg | Change From Baseline in Leukocytes, Neutrophils, Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets Levels | Leukocytes; Day 29; n= 16, 19, 17, 18, 17 | 0.20 10^12 cells/L | Standard Deviation 1.526 |
| Dapro 30 mg | Change From Baseline in Leukocytes, Neutrophils, Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets Levels | Eosinophils; Day 29; n= 16, 18, 17, 17, 15 | 0.007 10^12 cells/L | Standard Deviation 0.088 |
| Dapro 30 mg | Change From Baseline in Leukocytes, Neutrophils, Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets Levels | Lymphocytes; Day 15; n= 17, 19, 17, 21, 21 | -0.236 10^12 cells/L | Standard Deviation 0.4298 |
| Dapro 30 mg | Change From Baseline in Leukocytes, Neutrophils, Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets Levels | Leukocytes; Day 43; n= 16, 20, 19, 20, 19 | 0.67 10^12 cells/L | Standard Deviation 1.58 |
| Dapro 30 mg | Change From Baseline in Leukocytes, Neutrophils, Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets Levels | Monocytes; Day 15; n= 17, 19, 17, 21, 21 | -0.037 10^12 cells/L | Standard Deviation 0.146 |
| Dapro 30 mg | Change From Baseline in Leukocytes, Neutrophils, Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets Levels | Leukocytes; Day 15; n= 17, 19, 17, 21, 21 | -0.03 10^12 cells/L | Standard Deviation 1.463 |
| Dapro 30 mg | Change From Baseline in Leukocytes, Neutrophils, Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets Levels | Platelet; Day 29; n= 16, 18, 17, 17, 17 | -2.4 10^12 cells/L | Standard Deviation 33.65 |
Secondary
Change From Baseline in MCHC Levels
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in MCHC Levels | Day 15; n= 17, 19, 17, 21, 21 | 2.6 g/L | Standard Deviation 11.09 |
| Placebo | Change From Baseline in MCHC Levels | Day 43; n= 16, 20, 19, 21, 20 | 3.9 g/L | Standard Deviation 15.92 |
| Placebo | Change From Baseline in MCHC Levels | Day 29; n= 16, 19, 17, 18, 17 | 5.6 g/L | Standard Deviation 12.81 |
| Dapro 10 mg | Change From Baseline in MCHC Levels | Day 29; n= 16, 19, 17, 18, 17 | 7.3 g/L | Standard Deviation 16.92 |
| Dapro 10 mg | Change From Baseline in MCHC Levels | Day 15; n= 17, 19, 17, 21, 21 | 3.0 g/L | Standard Deviation 14.21 |
| Dapro 10 mg | Change From Baseline in MCHC Levels | Day 43; n= 16, 20, 19, 21, 20 | 3.0 g/L | Standard Deviation 16.53 |
| Dapro 15 mg | Change From Baseline in MCHC Levels | Day 29; n= 16, 19, 17, 18, 17 | 7.6 g/L | Standard Deviation 8.27 |
| Dapro 15 mg | Change From Baseline in MCHC Levels | Day 15; n= 17, 19, 17, 21, 21 | 3.5 g/L | Standard Deviation 10.87 |
| Dapro 15 mg | Change From Baseline in MCHC Levels | Day 43; n= 16, 20, 19, 21, 20 | 6.0 g/L | Standard Deviation 11.44 |
| Dapro 25 mg | Change From Baseline in MCHC Levels | Day 15; n= 17, 19, 17, 21, 21 | -3.2 g/L | Standard Deviation 11.48 |
| Dapro 25 mg | Change From Baseline in MCHC Levels | Day 43; n= 16, 20, 19, 21, 20 | -1.0 g/L | Standard Deviation 12.12 |
| Dapro 25 mg | Change From Baseline in MCHC Levels | Day 29; n= 16, 19, 17, 18, 17 | 0.8 g/L | Standard Deviation 10.04 |
| Dapro 30 mg | Change From Baseline in MCHC Levels | Day 29; n= 16, 19, 17, 18, 17 | -4.4 g/L | Standard Deviation 12.3 |
| Dapro 30 mg | Change From Baseline in MCHC Levels | Day 15; n= 17, 19, 17, 21, 21 | -5.0 g/L | Standard Deviation 12.92 |
| Dapro 30 mg | Change From Baseline in MCHC Levels | Day 43; n= 16, 20, 19, 21, 20 | -0.3 g/L | Standard Deviation 9.14 |
Secondary
Change From Baseline in MCH Levels
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in MCH Levels | Day 15; n= 17, 19, 17, 21, 21 | 0.16 Pg | Standard Deviation 0.602 |
| Placebo | Change From Baseline in MCH Levels | Day 43; n= 16, 20, 19, 21, 20 | 0.11 Pg | Standard Deviation 0.981 |
| Placebo | Change From Baseline in MCH Levels | Day 29; n= 16, 19, 17, 18, 17 | 0.16 Pg | Standard Deviation 0.982 |
| Dapro 10 mg | Change From Baseline in MCH Levels | Day 29; n= 16, 19, 17, 18, 17 | 0.58 Pg | Standard Deviation 1.185 |
| Dapro 10 mg | Change From Baseline in MCH Levels | Day 15; n= 17, 19, 17, 21, 21 | 0.19 Pg | Standard Deviation 0.817 |
| Dapro 10 mg | Change From Baseline in MCH Levels | Day 43; n= 16, 20, 19, 21, 20 | 0.13 Pg | Standard Deviation 0.948 |
| Dapro 15 mg | Change From Baseline in MCH Levels | Day 15; n= 17, 19, 17, 21, 21 | 0.27 Pg | Standard Deviation 0.685 |
| Dapro 15 mg | Change From Baseline in MCH Levels | Day 29; n= 16, 19, 17, 18, 17 | 0.42 Pg | Standard Deviation 0.824 |
| Dapro 15 mg | Change From Baseline in MCH Levels | Day 43; n= 16, 20, 19, 21, 20 | 0.34 Pg | Standard Deviation 0.993 |
| Dapro 25 mg | Change From Baseline in MCH Levels | Day 15; n= 17, 19, 17, 21, 21 | 0.16 Pg | Standard Deviation 0.52 |
| Dapro 25 mg | Change From Baseline in MCH Levels | Day 43; n= 16, 20, 19, 21, 20 | 0.11 Pg | Standard Deviation 0.842 |
| Dapro 25 mg | Change From Baseline in MCH Levels | Day 29; n= 16, 19, 17, 18, 17 | 0.41 Pg | Standard Deviation 0.744 |
| Dapro 30 mg | Change From Baseline in MCH Levels | Day 29; n= 16, 19, 17, 18, 17 | 0.15 Pg | Standard Deviation 0.987 |
| Dapro 30 mg | Change From Baseline in MCH Levels | Day 15; n= 17, 19, 17, 21, 21 | 0.25 Pg | Standard Deviation 0.87 |
| Dapro 30 mg | Change From Baseline in MCH Levels | Day 43; n= 16, 20, 19, 21, 20 | 0.29 Pg | Standard Deviation 0.809 |
Secondary
Change From Baseline in MCV Levels
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in MCV Levels | Day 29; n= 16, 19, 17, 18, 17 | -1.4 fL | Standard Deviation 3.24 |
| Placebo | Change From Baseline in MCV Levels | Day 15; n= 17, 19, 17, 21, 21 | -0.4 fL | Standard Deviation 2.98 |
| Placebo | Change From Baseline in MCV Levels | Day 43; n= 16, 20, 19, 21, 20 | -0.8 fL | Standard Deviation 3.15 |
| Dapro 10 mg | Change From Baseline in MCV Levels | Day 29; n= 16, 19, 17, 18, 17 | -0.5 fL | Standard Deviation 2.86 |
| Dapro 10 mg | Change From Baseline in MCV Levels | Day 43; n= 16, 20, 19, 21, 20 | -0.7 fL | Standard Deviation 3.37 |
| Dapro 10 mg | Change From Baseline in MCV Levels | Day 15; n= 17, 19, 17, 21, 21 | -0.2 fL | Standard Deviation 3.39 |
| Dapro 15 mg | Change From Baseline in MCV Levels | Day 15; n= 17, 19, 17, 21, 21 | -0.3 fL | Standard Deviation 2.57 |
| Dapro 15 mg | Change From Baseline in MCV Levels | Day 29; n= 16, 19, 17, 18, 17 | -0.9 fL | Standard Deviation 2.36 |
| Dapro 15 mg | Change From Baseline in MCV Levels | Day 43; n= 16, 20, 19, 21, 20 | -0.8 fL | Standard Deviation 3.28 |
| Dapro 25 mg | Change From Baseline in MCV Levels | Day 15; n= 17, 19, 17, 21, 21 | 1.3 fL | Standard Deviation 3.15 |
| Dapro 25 mg | Change From Baseline in MCV Levels | Day 43; n= 16, 20, 19, 21, 20 | 0.6 fL | Standard Deviation 3.06 |
| Dapro 25 mg | Change From Baseline in MCV Levels | Day 29; n= 16, 19, 17, 18, 17 | 0.9 fL | Standard Deviation 2.54 |
| Dapro 30 mg | Change From Baseline in MCV Levels | Day 29; n= 16, 19, 17, 18, 17 | 1.6 fL | Standard Deviation 2.4 |
| Dapro 30 mg | Change From Baseline in MCV Levels | Day 15; n= 17, 19, 17, 21, 21 | 2.2 fL | Standard Deviation 3.21 |
| Dapro 30 mg | Change From Baseline in MCV Levels | Day 43; n= 16, 20, 19, 21, 20 | 0.9 fL | Standard Deviation 2.1 |
Secondary
Change From Baseline in Pulse Rate Value at Pre-dialysis and Post-dialysis
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Pulse Rate Value at Pre-dialysis and Post-dialysis | Post-dialysis; Day 29; n= 17, 19, 18, 19, 17 | 4.2 Beats per minute | Standard Deviation 9.13 |
| Placebo | Change From Baseline in Pulse Rate Value at Pre-dialysis and Post-dialysis | Pre-dialysis; Day 15; n= 17, 20, 18, 22, 21 | 7.0 Beats per minute | Standard Deviation 9.5 |
| Placebo | Change From Baseline in Pulse Rate Value at Pre-dialysis and Post-dialysis | Pre-dialysis; Day 43; n= 16, 20, 19, 21, 21 | 3.1 Beats per minute | Standard Deviation 9.59 |
| Placebo | Change From Baseline in Pulse Rate Value at Pre-dialysis and Post-dialysis | Post-dialysis; Day 15; n= 17, 20, 18, 22, 21 | 2.2 Beats per minute | Standard Deviation 11.61 |
| Placebo | Change From Baseline in Pulse Rate Value at Pre-dialysis and Post-dialysis | Post-dialysis; Day 43; n= 16, 20, 19, 21, 21 | 2.3 Beats per minute | Standard Deviation 8.67 |
| Placebo | Change From Baseline in Pulse Rate Value at Pre-dialysis and Post-dialysis | Pre-dialysis; Day 29; n= 17, 19, 18, 19, 17 | 2.4 Beats per minute | Standard Deviation 6.92 |
| Dapro 10 mg | Change From Baseline in Pulse Rate Value at Pre-dialysis and Post-dialysis | Pre-dialysis; Day 15; n= 17, 20, 18, 22, 21 | -2.6 Beats per minute | Standard Deviation 8.46 |
| Dapro 10 mg | Change From Baseline in Pulse Rate Value at Pre-dialysis and Post-dialysis | Post-dialysis; Day 29; n= 17, 19, 18, 19, 17 | 1.5 Beats per minute | Standard Deviation 13.13 |
| Dapro 10 mg | Change From Baseline in Pulse Rate Value at Pre-dialysis and Post-dialysis | Pre-dialysis; Day 29; n= 17, 19, 18, 19, 17 | 0.9 Beats per minute | Standard Deviation 12.86 |
| Dapro 10 mg | Change From Baseline in Pulse Rate Value at Pre-dialysis and Post-dialysis | Post-dialysis; Day 43; n= 16, 20, 19, 21, 21 | 0.3 Beats per minute | Standard Deviation 12.96 |
| Dapro 10 mg | Change From Baseline in Pulse Rate Value at Pre-dialysis and Post-dialysis | Pre-dialysis; Day 43; n= 16, 20, 19, 21, 21 | 0.1 Beats per minute | Standard Deviation 6.57 |
| Dapro 10 mg | Change From Baseline in Pulse Rate Value at Pre-dialysis and Post-dialysis | Post-dialysis; Day 15; n= 17, 20, 18, 22, 21 | -1.2 Beats per minute | Standard Deviation 12.86 |
| Dapro 15 mg | Change From Baseline in Pulse Rate Value at Pre-dialysis and Post-dialysis | Pre-dialysis; Day 43; n= 16, 20, 19, 21, 21 | 0.8 Beats per minute | Standard Deviation 6.11 |
| Dapro 15 mg | Change From Baseline in Pulse Rate Value at Pre-dialysis and Post-dialysis | Pre-dialysis; Day 29; n= 17, 19, 18, 19, 17 | 3.4 Beats per minute | Standard Deviation 7.58 |
| Dapro 15 mg | Change From Baseline in Pulse Rate Value at Pre-dialysis and Post-dialysis | Pre-dialysis; Day 15; n= 17, 20, 18, 22, 21 | 2.3 Beats per minute | Standard Deviation 5.76 |
| Dapro 15 mg | Change From Baseline in Pulse Rate Value at Pre-dialysis and Post-dialysis | Post-dialysis; Day 29; n= 17, 19, 18, 19, 17 | -0.8 Beats per minute | Standard Deviation 9.79 |
| Dapro 15 mg | Change From Baseline in Pulse Rate Value at Pre-dialysis and Post-dialysis | Post-dialysis; Day 43; n= 16, 20, 19, 21, 21 | -0.8 Beats per minute | Standard Deviation 9.32 |
| Dapro 15 mg | Change From Baseline in Pulse Rate Value at Pre-dialysis and Post-dialysis | Post-dialysis; Day 15; n= 17, 20, 18, 22, 21 | 1.1 Beats per minute | Standard Deviation 10.15 |
| Dapro 25 mg | Change From Baseline in Pulse Rate Value at Pre-dialysis and Post-dialysis | Pre-dialysis; Day 15; n= 17, 20, 18, 22, 21 | 0.7 Beats per minute | Standard Deviation 11.46 |
| Dapro 25 mg | Change From Baseline in Pulse Rate Value at Pre-dialysis and Post-dialysis | Pre-dialysis; Day 29; n= 17, 19, 18, 19, 17 | 0.5 Beats per minute | Standard Deviation 10.01 |
| Dapro 25 mg | Change From Baseline in Pulse Rate Value at Pre-dialysis and Post-dialysis | Pre-dialysis; Day 43; n= 16, 20, 19, 21, 21 | -0.6 Beats per minute | Standard Deviation 10.03 |
| Dapro 25 mg | Change From Baseline in Pulse Rate Value at Pre-dialysis and Post-dialysis | Post-dialysis; Day 15; n= 17, 20, 18, 22, 21 | 0.5 Beats per minute | Standard Deviation 8 |
| Dapro 25 mg | Change From Baseline in Pulse Rate Value at Pre-dialysis and Post-dialysis | Post-dialysis; Day 29; n= 17, 19, 18, 19, 17 | 2.6 Beats per minute | Standard Deviation 9.04 |
| Dapro 25 mg | Change From Baseline in Pulse Rate Value at Pre-dialysis and Post-dialysis | Post-dialysis; Day 43; n= 16, 20, 19, 21, 21 | -0.1 Beats per minute | Standard Deviation 9.08 |
| Dapro 30 mg | Change From Baseline in Pulse Rate Value at Pre-dialysis and Post-dialysis | Post-dialysis; Day 29; n= 17, 19, 18, 19, 17 | 6.0 Beats per minute | Standard Deviation 7.5 |
| Dapro 30 mg | Change From Baseline in Pulse Rate Value at Pre-dialysis and Post-dialysis | Pre-dialysis; Day 43; n= 16, 20, 19, 21, 21 | 0.2 Beats per minute | Standard Deviation 6.79 |
| Dapro 30 mg | Change From Baseline in Pulse Rate Value at Pre-dialysis and Post-dialysis | Pre-dialysis; Day 29; n= 17, 19, 18, 19, 17 | -3.0 Beats per minute | Standard Deviation 9.14 |
| Dapro 30 mg | Change From Baseline in Pulse Rate Value at Pre-dialysis and Post-dialysis | Pre-dialysis; Day 15; n= 17, 20, 18, 22, 21 | -1.4 Beats per minute | Standard Deviation 11.15 |
| Dapro 30 mg | Change From Baseline in Pulse Rate Value at Pre-dialysis and Post-dialysis | Post-dialysis; Day 15; n= 17, 20, 18, 22, 21 | 4.4 Beats per minute | Standard Deviation 13.28 |
| Dapro 30 mg | Change From Baseline in Pulse Rate Value at Pre-dialysis and Post-dialysis | Post-dialysis; Day 43; n= 16, 20, 19, 21, 21 | 3.9 Beats per minute | Standard Deviation 9.32 |
Secondary
Change From Baseline in Red Blood Cell (RBC) Count
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
Population: ITT Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Red Blood Cell (RBC) Count | -0.19 10^12 cells/L | Standard Deviation 0.263 |
| Dapro 10 mg | Change From Baseline in Red Blood Cell (RBC) Count | -0.12 10^12 cells/L | Standard Deviation 0.494 |
| Dapro 15 mg | Change From Baseline in Red Blood Cell (RBC) Count | -0.13 10^12 cells/L | Standard Deviation 0.5 |
| Dapro 25 mg | Change From Baseline in Red Blood Cell (RBC) Count | 0.12 10^12 cells/L | Standard Deviation 0.42 |
| Dapro 30 mg | Change From Baseline in Red Blood Cell (RBC) Count | 0.15 10^12 cells/L | Standard Deviation 0.342 |
Secondary
Change From Baseline in Reticulocyte Count
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
Population: ITT Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Reticulocyte Count | -0.08 Percentage of reticulocyte | Standard Deviation 0.848 |
| Dapro 10 mg | Change From Baseline in Reticulocyte Count | -0.11 Percentage of reticulocyte | Standard Deviation 0.803 |
| Dapro 15 mg | Change From Baseline in Reticulocyte Count | -0.04 Percentage of reticulocyte | Standard Deviation 0.581 |
| Dapro 25 mg | Change From Baseline in Reticulocyte Count | 0.43 Percentage of reticulocyte | Standard Deviation 0.547 |
| Dapro 30 mg | Change From Baseline in Reticulocyte Count | 0.09 Percentage of reticulocyte | Standard Deviation 0.695 |
Secondary
Change From Baseline in Reticulocyte Hemoglobin (CHr)
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
Population: ITT Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Reticulocyte Hemoglobin (CHr) | -0.15 Picograms (pg) | Standard Deviation 1.375 |
| Dapro 10 mg | Change From Baseline in Reticulocyte Hemoglobin (CHr) | 0.23 Picograms (pg) | Standard Deviation 1.335 |
| Dapro 15 mg | Change From Baseline in Reticulocyte Hemoglobin (CHr) | 0.26 Picograms (pg) | Standard Deviation 1.103 |
| Dapro 25 mg | Change From Baseline in Reticulocyte Hemoglobin (CHr) | 0.23 Picograms (pg) | Standard Deviation 1.04 |
| Dapro 30 mg | Change From Baseline in Reticulocyte Hemoglobin (CHr) | 0.59 Picograms (pg) | Standard Deviation 1.436 |
Secondary
Change From Baseline in SBP and DBP Values at Pre-dialysis and Post-dialysis
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in SBP and DBP Values at Pre-dialysis and Post-dialysis | DBP; pre-dialysis; Day 43; n= 16, 20, 19, 21, 21 | 2.2 mmHg | Standard Deviation 8.8 |
| Placebo | Change From Baseline in SBP and DBP Values at Pre-dialysis and Post-dialysis | DBP; pre-dialysis; Day 15; n= 17, 20, 18, 22, 21 | 1.1 mmHg | Standard Deviation 10.57 |
| Placebo | Change From Baseline in SBP and DBP Values at Pre-dialysis and Post-dialysis | DBP; post-dialysis; Day 29; n= 17, 19, 18, 19, 17 | 3.7 mmHg | Standard Deviation 12.93 |
| Placebo | Change From Baseline in SBP and DBP Values at Pre-dialysis and Post-dialysis | DBP; post-dialysis; Day 15; n= 17, 20, 18, 22, 21 | 2.4 mmHg | Standard Deviation 11.41 |
| Placebo | Change From Baseline in SBP and DBP Values at Pre-dialysis and Post-dialysis | SBP; post-dialysis; Day 43; n= 16, 20, 19, 21, 21 | 3.1 mmHg | Standard Deviation 22.22 |
| Placebo | Change From Baseline in SBP and DBP Values at Pre-dialysis and Post-dialysis | SBP; post-dialysis; Day 29; n= 17, 19, 18, 19, 17 | 2.3 mmHg | Standard Deviation 19.72 |
| Placebo | Change From Baseline in SBP and DBP Values at Pre-dialysis and Post-dialysis | SBP; post-dialysis; Day 15; n= 17, 20, 18, 22, 21 | 5.4 mmHg | Standard Deviation 21.39 |
| Placebo | Change From Baseline in SBP and DBP Values at Pre-dialysis and Post-dialysis | DBP; pre-dialysis; Day 29; n= 17, 19, 18, 19, 17 | -0.3 mmHg | Standard Deviation 11.09 |
| Placebo | Change From Baseline in SBP and DBP Values at Pre-dialysis and Post-dialysis | DBP; post-dialysis; Day 43; n= 16, 20, 19, 21, 21 | -0.6 mmHg | Standard Deviation 10.07 |
| Placebo | Change From Baseline in SBP and DBP Values at Pre-dialysis and Post-dialysis | SBP; pre-dialysis; Day 43; n= 16, 20, 19, 21, 21 | -2.1 mmHg | Standard Deviation 21.34 |
| Placebo | Change From Baseline in SBP and DBP Values at Pre-dialysis and Post-dialysis | SBP; pre-dialysis; Day 29; n= 17, 19, 18, 19, 17 | -0.6 mmHg | Standard Deviation 20.32 |
| Placebo | Change From Baseline in SBP and DBP Values at Pre-dialysis and Post-dialysis | SBP; pre-dialysis; Day 15; n= 17, 20, 18, 22, 21 | -2.9 mmHg | Standard Deviation 22.03 |
| Dapro 10 mg | Change From Baseline in SBP and DBP Values at Pre-dialysis and Post-dialysis | DBP; post-dialysis; Day 29; n= 17, 19, 18, 19, 17 | -2.5 mmHg | Standard Deviation 8.52 |
| Dapro 10 mg | Change From Baseline in SBP and DBP Values at Pre-dialysis and Post-dialysis | DBP; pre-dialysis; Day 15; n= 17, 20, 18, 22, 21 | 1.2 mmHg | Standard Deviation 8.85 |
| Dapro 10 mg | Change From Baseline in SBP and DBP Values at Pre-dialysis and Post-dialysis | DBP; pre-dialysis; Day 29; n= 17, 19, 18, 19, 17 | -4.7 mmHg | Standard Deviation 10.04 |
| Dapro 10 mg | Change From Baseline in SBP and DBP Values at Pre-dialysis and Post-dialysis | DBP; pre-dialysis; Day 43; n= 16, 20, 19, 21, 21 | -2.0 mmHg | Standard Deviation 9.47 |
| Dapro 10 mg | Change From Baseline in SBP and DBP Values at Pre-dialysis and Post-dialysis | DBP; post-dialysis; Day 15; n= 17, 20, 18, 22, 21 | 2.4 mmHg | Standard Deviation 7.71 |
| Dapro 10 mg | Change From Baseline in SBP and DBP Values at Pre-dialysis and Post-dialysis | DBP; post-dialysis; Day 43; n= 16, 20, 19, 21, 21 | -0.3 mmHg | Standard Deviation 9.53 |
| Dapro 10 mg | Change From Baseline in SBP and DBP Values at Pre-dialysis and Post-dialysis | SBP; pre-dialysis; Day 15; n= 17, 20, 18, 22, 21 | 1.7 mmHg | Standard Deviation 14.14 |
| Dapro 10 mg | Change From Baseline in SBP and DBP Values at Pre-dialysis and Post-dialysis | SBP; pre-dialysis; Day 29; n= 17, 19, 18, 19, 17 | -3.9 mmHg | Standard Deviation 19.72 |
| Dapro 10 mg | Change From Baseline in SBP and DBP Values at Pre-dialysis and Post-dialysis | SBP; pre-dialysis; Day 43; n= 16, 20, 19, 21, 21 | 1.2 mmHg | Standard Deviation 17.14 |
| Dapro 10 mg | Change From Baseline in SBP and DBP Values at Pre-dialysis and Post-dialysis | SBP; post-dialysis; Day 15; n= 17, 20, 18, 22, 21 | -3.6 mmHg | Standard Deviation 20.13 |
| Dapro 10 mg | Change From Baseline in SBP and DBP Values at Pre-dialysis and Post-dialysis | SBP; post-dialysis; Day 29; n= 17, 19, 18, 19, 17 | -9.4 mmHg | Standard Deviation 18.5 |
| Dapro 10 mg | Change From Baseline in SBP and DBP Values at Pre-dialysis and Post-dialysis | SBP; post-dialysis; Day 43; n= 16, 20, 19, 21, 21 | -3.2 mmHg | Standard Deviation 21.71 |
| Dapro 15 mg | Change From Baseline in SBP and DBP Values at Pre-dialysis and Post-dialysis | DBP; post-dialysis; Day 29; n= 17, 19, 18, 19, 17 | -3.2 mmHg | Standard Deviation 11.61 |
| Dapro 15 mg | Change From Baseline in SBP and DBP Values at Pre-dialysis and Post-dialysis | DBP; post-dialysis; Day 43; n= 16, 20, 19, 21, 21 | -3.8 mmHg | Standard Deviation 12.13 |
| Dapro 15 mg | Change From Baseline in SBP and DBP Values at Pre-dialysis and Post-dialysis | SBP; pre-dialysis; Day 15; n= 17, 20, 18, 22, 21 | -5.6 mmHg | Standard Deviation 14.77 |
| Dapro 15 mg | Change From Baseline in SBP and DBP Values at Pre-dialysis and Post-dialysis | DBP; pre-dialysis; Day 15; n= 17, 20, 18, 22, 21 | -1.7 mmHg | Standard Deviation 9.78 |
| Dapro 15 mg | Change From Baseline in SBP and DBP Values at Pre-dialysis and Post-dialysis | SBP; pre-dialysis; Day 29; n= 17, 19, 18, 19, 17 | -4.7 mmHg | Standard Deviation 18.17 |
| Dapro 15 mg | Change From Baseline in SBP and DBP Values at Pre-dialysis and Post-dialysis | DBP; pre-dialysis; Day 29; n= 17, 19, 18, 19, 17 | -3.0 mmHg | Standard Deviation 8.99 |
| Dapro 15 mg | Change From Baseline in SBP and DBP Values at Pre-dialysis and Post-dialysis | SBP; pre-dialysis; Day 43; n= 16, 20, 19, 21, 21 | -6.2 mmHg | Standard Deviation 13.83 |
| Dapro 15 mg | Change From Baseline in SBP and DBP Values at Pre-dialysis and Post-dialysis | SBP; post-dialysis; Day 43; n= 16, 20, 19, 21, 21 | -3.6 mmHg | Standard Deviation 17.88 |
| Dapro 15 mg | Change From Baseline in SBP and DBP Values at Pre-dialysis and Post-dialysis | SBP; post-dialysis; Day 15; n= 17, 20, 18, 22, 21 | 6.1 mmHg | Standard Deviation 20.81 |
| Dapro 15 mg | Change From Baseline in SBP and DBP Values at Pre-dialysis and Post-dialysis | SBP; post-dialysis; Day 29; n= 17, 19, 18, 19, 17 | 0.8 mmHg | Standard Deviation 24.79 |
| Dapro 15 mg | Change From Baseline in SBP and DBP Values at Pre-dialysis and Post-dialysis | DBP; post-dialysis; Day 15; n= 17, 20, 18, 22, 21 | -2.9 mmHg | Standard Deviation 11.11 |
| Dapro 15 mg | Change From Baseline in SBP and DBP Values at Pre-dialysis and Post-dialysis | DBP; pre-dialysis; Day 43; n= 16, 20, 19, 21, 21 | -3.1 mmHg | Standard Deviation 11.06 |
| Dapro 25 mg | Change From Baseline in SBP and DBP Values at Pre-dialysis and Post-dialysis | DBP; pre-dialysis; Day 29; n= 17, 19, 18, 19, 17 | 1.4 mmHg | Standard Deviation 10.5 |
| Dapro 25 mg | Change From Baseline in SBP and DBP Values at Pre-dialysis and Post-dialysis | SBP; pre-dialysis; Day 29; n= 17, 19, 18, 19, 17 | 1.3 mmHg | Standard Deviation 17.51 |
| Dapro 25 mg | Change From Baseline in SBP and DBP Values at Pre-dialysis and Post-dialysis | DBP; pre-dialysis; Day 43; n= 16, 20, 19, 21, 21 | 5.2 mmHg | Standard Deviation 15.08 |
| Dapro 25 mg | Change From Baseline in SBP and DBP Values at Pre-dialysis and Post-dialysis | SBP; pre-dialysis; Day 43; n= 16, 20, 19, 21, 21 | 3.3 mmHg | Standard Deviation 19.47 |
| Dapro 25 mg | Change From Baseline in SBP and DBP Values at Pre-dialysis and Post-dialysis | SBP; post-dialysis; Day 43; n= 16, 20, 19, 21, 21 | 12.0 mmHg | Standard Deviation 20.19 |
| Dapro 25 mg | Change From Baseline in SBP and DBP Values at Pre-dialysis and Post-dialysis | DBP; post-dialysis; Day 15; n= 17, 20, 18, 22, 21 | 3.6 mmHg | Standard Deviation 9.84 |
| Dapro 25 mg | Change From Baseline in SBP and DBP Values at Pre-dialysis and Post-dialysis | SBP; post-dialysis; Day 15; n= 17, 20, 18, 22, 21 | 5.7 mmHg | Standard Deviation 21.07 |
| Dapro 25 mg | Change From Baseline in SBP and DBP Values at Pre-dialysis and Post-dialysis | DBP; post-dialysis; Day 29; n= 17, 19, 18, 19, 17 | 4.1 mmHg | Standard Deviation 9.33 |
| Dapro 25 mg | Change From Baseline in SBP and DBP Values at Pre-dialysis and Post-dialysis | SBP; post-dialysis; Day 29; n= 17, 19, 18, 19, 17 | 9.3 mmHg | Standard Deviation 19.03 |
| Dapro 25 mg | Change From Baseline in SBP and DBP Values at Pre-dialysis and Post-dialysis | DBP; post-dialysis; Day 43; n= 16, 20, 19, 21, 21 | 4.5 mmHg | Standard Deviation 9.99 |
| Dapro 25 mg | Change From Baseline in SBP and DBP Values at Pre-dialysis and Post-dialysis | DBP; pre-dialysis; Day 15; n= 17, 20, 18, 22, 21 | 1.8 mmHg | Standard Deviation 12.68 |
| Dapro 25 mg | Change From Baseline in SBP and DBP Values at Pre-dialysis and Post-dialysis | SBP; pre-dialysis; Day 15; n= 17, 20, 18, 22, 21 | 2.5 mmHg | Standard Deviation 20.68 |
| Dapro 30 mg | Change From Baseline in SBP and DBP Values at Pre-dialysis and Post-dialysis | DBP; pre-dialysis; Day 29; n= 17, 19, 18, 19, 17 | -0.1 mmHg | Standard Deviation 13.8 |
| Dapro 30 mg | Change From Baseline in SBP and DBP Values at Pre-dialysis and Post-dialysis | DBP; pre-dialysis; Day 43; n= 16, 20, 19, 21, 21 | 2.1 mmHg | Standard Deviation 11 |
| Dapro 30 mg | Change From Baseline in SBP and DBP Values at Pre-dialysis and Post-dialysis | SBP; post-dialysis; Day 29; n= 17, 19, 18, 19, 17 | 4.0 mmHg | Standard Deviation 19.76 |
| Dapro 30 mg | Change From Baseline in SBP and DBP Values at Pre-dialysis and Post-dialysis | SBP; pre-dialysis; Day 29; n= 17, 19, 18, 19, 17 | 4.5 mmHg | Standard Deviation 20.03 |
| Dapro 30 mg | Change From Baseline in SBP and DBP Values at Pre-dialysis and Post-dialysis | SBP; pre-dialysis; Day 15; n= 17, 20, 18, 22, 21 | -1.4 mmHg | Standard Deviation 16.35 |
| Dapro 30 mg | Change From Baseline in SBP and DBP Values at Pre-dialysis and Post-dialysis | DBP; post-dialysis; Day 29; n= 17, 19, 18, 19, 17 | 0.2 mmHg | Standard Deviation 10.59 |
| Dapro 30 mg | Change From Baseline in SBP and DBP Values at Pre-dialysis and Post-dialysis | DBP; post-dialysis; Day 15; n= 17, 20, 18, 22, 21 | -0.8 mmHg | Standard Deviation 14.13 |
| Dapro 30 mg | Change From Baseline in SBP and DBP Values at Pre-dialysis and Post-dialysis | SBP; post-dialysis; Day 15; n= 17, 20, 18, 22, 21 | -0.7 mmHg | Standard Deviation 22.33 |
| Dapro 30 mg | Change From Baseline in SBP and DBP Values at Pre-dialysis and Post-dialysis | SBP; pre-dialysis; Day 43; n= 16, 20, 19, 21, 21 | 4.3 mmHg | Standard Deviation 10.03 |
| Dapro 30 mg | Change From Baseline in SBP and DBP Values at Pre-dialysis and Post-dialysis | DBP; pre-dialysis; Day 15; n= 17, 20, 18, 22, 21 | -2.1 mmHg | Standard Deviation 11.04 |
| Dapro 30 mg | Change From Baseline in SBP and DBP Values at Pre-dialysis and Post-dialysis | SBP; post-dialysis; Day 43; n= 16, 20, 19, 21, 21 | 4.7 mmHg | Standard Deviation 20.11 |
| Dapro 30 mg | Change From Baseline in SBP and DBP Values at Pre-dialysis and Post-dialysis | DBP; post-dialysis; Day 43; n= 16, 20, 19, 21, 21 | 4.8 mmHg | Standard Deviation 10.28 |
Secondary
Change From Baseline in Sodium, Potassium, Glucose, Calcium and Phosphate Levels
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Sodium, Potassium, Glucose, Calcium and Phosphate Levels | Glucose; Day 43; n= 15, 20, 18, 21, 21 | 0.23 Mmol/L | Standard Deviation 1.335 |
| Placebo | Change From Baseline in Sodium, Potassium, Glucose, Calcium and Phosphate Levels | Potassium; Day 43; n= 15, 20, 18, 21, 21 | 0.04 Mmol/L | Standard Deviation 0.565 |
| Placebo | Change From Baseline in Sodium, Potassium, Glucose, Calcium and Phosphate Levels | Sodium; Day 15; n= 17, 20, 18, 22, 20 | -0.9 Mmol/L | Standard Deviation 2.73 |
| Placebo | Change From Baseline in Sodium, Potassium, Glucose, Calcium and Phosphate Levels | Glucose; Day 29; n= 17, 19, 18, 19, 17 | 1.48 Mmol/L | Standard Deviation 3.771 |
| Placebo | Change From Baseline in Sodium, Potassium, Glucose, Calcium and Phosphate Levels | Glucose; Day 15; n= 17, 20, 18, 22, 20 | 1.14 Mmol/L | Standard Deviation 3.339 |
| Placebo | Change From Baseline in Sodium, Potassium, Glucose, Calcium and Phosphate Levels | Sodium; Day 43; n= 15, 20, 18, 21, 21 | 0.7 Mmol/L | Standard Deviation 2.06 |
| Placebo | Change From Baseline in Sodium, Potassium, Glucose, Calcium and Phosphate Levels | Phosphate; Day 43; n= 15, 20, 18, 21, 21 | -0.067 Mmol/L | Standard Deviation 0.4337 |
| Placebo | Change From Baseline in Sodium, Potassium, Glucose, Calcium and Phosphate Levels | Sodium; Day 29; n= 17, 19, 18, 19, 17 | -1.1 Mmol/L | Standard Deviation 2.26 |
| Placebo | Change From Baseline in Sodium, Potassium, Glucose, Calcium and Phosphate Levels | Phosphate; Day 29; n= 17, 19, 18, 19, 17 | 0.091 Mmol/L | Standard Deviation 0.3882 |
| Placebo | Change From Baseline in Sodium, Potassium, Glucose, Calcium and Phosphate Levels | Phosphate; Day 15; n= 17, 20, 18, 22, 20 | -0.091 Mmol/L | Standard Deviation 0.4051 |
| Placebo | Change From Baseline in Sodium, Potassium, Glucose, Calcium and Phosphate Levels | Calcium; Day 43; n= 15, 20, 18, 21, 21 | -0.015 Mmol/L | Standard Deviation 0.1576 |
| Placebo | Change From Baseline in Sodium, Potassium, Glucose, Calcium and Phosphate Levels | Potassium; Day 29; n= 17, 19, 18, 19, 17 | 0.20 Mmol/L | Standard Deviation 0.744 |
| Placebo | Change From Baseline in Sodium, Potassium, Glucose, Calcium and Phosphate Levels | Potassium; Day 15; n= 17, 20, 18, 22, 20 | 0.04 Mmol/L | Standard Deviation 0.462 |
| Placebo | Change From Baseline in Sodium, Potassium, Glucose, Calcium and Phosphate Levels | Calcium; Day 29; n= 17, 19, 18, 19, 17 | -0.054 Mmol/L | Standard Deviation 0.1486 |
| Placebo | Change From Baseline in Sodium, Potassium, Glucose, Calcium and Phosphate Levels | Calcium; Day 15; n= 17, 20, 18, 22, 20 | -0.011 Mmol/L | Standard Deviation 0.1227 |
| Dapro 10 mg | Change From Baseline in Sodium, Potassium, Glucose, Calcium and Phosphate Levels | Sodium; Day 43; n= 15, 20, 18, 21, 21 | 0.1 Mmol/L | Standard Deviation 2.35 |
| Dapro 10 mg | Change From Baseline in Sodium, Potassium, Glucose, Calcium and Phosphate Levels | Sodium; Day 15; n= 17, 20, 18, 22, 20 | -0.6 Mmol/L | Standard Deviation 2.62 |
| Dapro 10 mg | Change From Baseline in Sodium, Potassium, Glucose, Calcium and Phosphate Levels | Potassium; Day 15; n= 17, 20, 18, 22, 20 | 0.05 Mmol/L | Standard Deviation 0.526 |
| Dapro 10 mg | Change From Baseline in Sodium, Potassium, Glucose, Calcium and Phosphate Levels | Potassium; Day 29; n= 17, 19, 18, 19, 17 | 0.05 Mmol/L | Standard Deviation 0.66 |
| Dapro 10 mg | Change From Baseline in Sodium, Potassium, Glucose, Calcium and Phosphate Levels | Potassium; Day 43; n= 15, 20, 18, 21, 21 | -0.05 Mmol/L | Standard Deviation 0.674 |
| Dapro 10 mg | Change From Baseline in Sodium, Potassium, Glucose, Calcium and Phosphate Levels | Glucose; Day 15; n= 17, 20, 18, 22, 20 | 0.51 Mmol/L | Standard Deviation 2.959 |
| Dapro 10 mg | Change From Baseline in Sodium, Potassium, Glucose, Calcium and Phosphate Levels | Glucose; Day 29; n= 17, 19, 18, 19, 17 | 0.70 Mmol/L | Standard Deviation 3.756 |
| Dapro 10 mg | Change From Baseline in Sodium, Potassium, Glucose, Calcium and Phosphate Levels | Glucose; Day 43; n= 15, 20, 18, 21, 21 | 0.06 Mmol/L | Standard Deviation 3.072 |
| Dapro 10 mg | Change From Baseline in Sodium, Potassium, Glucose, Calcium and Phosphate Levels | Calcium; Day 15; n= 17, 20, 18, 22, 20 | -0.051 Mmol/L | Standard Deviation 0.1354 |
| Dapro 10 mg | Change From Baseline in Sodium, Potassium, Glucose, Calcium and Phosphate Levels | Calcium; Day 29; n= 17, 19, 18, 19, 17 | -0.025 Mmol/L | Standard Deviation 0.1129 |
| Dapro 10 mg | Change From Baseline in Sodium, Potassium, Glucose, Calcium and Phosphate Levels | Calcium; Day 43; n= 15, 20, 18, 21, 21 | -0.035 Mmol/L | Standard Deviation 0.1261 |
| Dapro 10 mg | Change From Baseline in Sodium, Potassium, Glucose, Calcium and Phosphate Levels | Phosphate; Day 15; n= 17, 20, 18, 22, 20 | 0.183 Mmol/L | Standard Deviation 0.5184 |
| Dapro 10 mg | Change From Baseline in Sodium, Potassium, Glucose, Calcium and Phosphate Levels | Phosphate; Day 29; n= 17, 19, 18, 19, 17 | 0.011 Mmol/L | Standard Deviation 0.4932 |
| Dapro 10 mg | Change From Baseline in Sodium, Potassium, Glucose, Calcium and Phosphate Levels | Phosphate; Day 43; n= 15, 20, 18, 21, 21 | -0.068 Mmol/L | Standard Deviation 0.5324 |
| Dapro 10 mg | Change From Baseline in Sodium, Potassium, Glucose, Calcium and Phosphate Levels | Sodium; Day 29; n= 17, 19, 18, 19, 17 | -1.2 Mmol/L | Standard Deviation 3.08 |
| Dapro 15 mg | Change From Baseline in Sodium, Potassium, Glucose, Calcium and Phosphate Levels | Phosphate; Day 29; n= 17, 19, 18, 19, 17 | 0.069 Mmol/L | Standard Deviation 0.495 |
| Dapro 15 mg | Change From Baseline in Sodium, Potassium, Glucose, Calcium and Phosphate Levels | Potassium; Day 15; n= 17, 20, 18, 22, 20 | -0.09 Mmol/L | Standard Deviation 1.099 |
| Dapro 15 mg | Change From Baseline in Sodium, Potassium, Glucose, Calcium and Phosphate Levels | Sodium; Day 29; n= 17, 19, 18, 19, 17 | -0.9 Mmol/L | Standard Deviation 2.26 |
| Dapro 15 mg | Change From Baseline in Sodium, Potassium, Glucose, Calcium and Phosphate Levels | Calcium; Day 43; n= 15, 20, 18, 21, 21 | 0.018 Mmol/L | Standard Deviation 0.1852 |
| Dapro 15 mg | Change From Baseline in Sodium, Potassium, Glucose, Calcium and Phosphate Levels | Glucose; Day 15; n= 17, 20, 18, 22, 20 | 0.45 Mmol/L | Standard Deviation 1.74 |
| Dapro 15 mg | Change From Baseline in Sodium, Potassium, Glucose, Calcium and Phosphate Levels | Phosphate; Day 15; n= 17, 20, 18, 22, 20 | 0.111 Mmol/L | Standard Deviation 0.5715 |
| Dapro 15 mg | Change From Baseline in Sodium, Potassium, Glucose, Calcium and Phosphate Levels | Potassium; Day 43; n= 15, 20, 18, 21, 21 | -0.06 Mmol/L | Standard Deviation 1.004 |
| Dapro 15 mg | Change From Baseline in Sodium, Potassium, Glucose, Calcium and Phosphate Levels | Phosphate; Day 43; n= 15, 20, 18, 21, 21 | -0.053 Mmol/L | Standard Deviation 0.54 |
| Dapro 15 mg | Change From Baseline in Sodium, Potassium, Glucose, Calcium and Phosphate Levels | Calcium; Day 15; n= 17, 20, 18, 22, 20 | -0.026 Mmol/L | Standard Deviation 0.1439 |
| Dapro 15 mg | Change From Baseline in Sodium, Potassium, Glucose, Calcium and Phosphate Levels | Glucose; Day 43; n= 15, 20, 18, 21, 21 | 0.52 Mmol/L | Standard Deviation 1.383 |
| Dapro 15 mg | Change From Baseline in Sodium, Potassium, Glucose, Calcium and Phosphate Levels | Sodium; Day 15; n= 17, 20, 18, 22, 20 | -0.5 Mmol/L | Standard Deviation 2.64 |
| Dapro 15 mg | Change From Baseline in Sodium, Potassium, Glucose, Calcium and Phosphate Levels | Potassium; Day 29; n= 17, 19, 18, 19, 17 | -0.14 Mmol/L | Standard Deviation 0.651 |
| Dapro 15 mg | Change From Baseline in Sodium, Potassium, Glucose, Calcium and Phosphate Levels | Sodium; Day 43; n= 15, 20, 18, 21, 21 | -0.6 Mmol/L | Standard Deviation 2.28 |
| Dapro 15 mg | Change From Baseline in Sodium, Potassium, Glucose, Calcium and Phosphate Levels | Calcium; Day 29; n= 17, 19, 18, 19, 17 | -0.009 Mmol/L | Standard Deviation 0.1556 |
| Dapro 15 mg | Change From Baseline in Sodium, Potassium, Glucose, Calcium and Phosphate Levels | Glucose; Day 29; n= 17, 19, 18, 19, 17 | 0.73 Mmol/L | Standard Deviation 1.135 |
| Dapro 25 mg | Change From Baseline in Sodium, Potassium, Glucose, Calcium and Phosphate Levels | Glucose; Day 29; n= 17, 19, 18, 19, 17 | 0.61 Mmol/L | Standard Deviation 4.188 |
| Dapro 25 mg | Change From Baseline in Sodium, Potassium, Glucose, Calcium and Phosphate Levels | Glucose; Day 43; n= 15, 20, 18, 21, 21 | -0.81 Mmol/L | Standard Deviation 2.516 |
| Dapro 25 mg | Change From Baseline in Sodium, Potassium, Glucose, Calcium and Phosphate Levels | Potassium; Day 29; n= 17, 19, 18, 19, 17 | 0.02 Mmol/L | Standard Deviation 0.64 |
| Dapro 25 mg | Change From Baseline in Sodium, Potassium, Glucose, Calcium and Phosphate Levels | Calcium; Day 15; n= 17, 20, 18, 22, 20 | -0.031 Mmol/L | Standard Deviation 0.0956 |
| Dapro 25 mg | Change From Baseline in Sodium, Potassium, Glucose, Calcium and Phosphate Levels | Calcium; Day 29; n= 17, 19, 18, 19, 17 | -0.012 Mmol/L | Standard Deviation 0.0939 |
| Dapro 25 mg | Change From Baseline in Sodium, Potassium, Glucose, Calcium and Phosphate Levels | Calcium; Day 43; n= 15, 20, 18, 21, 21 | 0.001 Mmol/L | Standard Deviation 0.0742 |
| Dapro 25 mg | Change From Baseline in Sodium, Potassium, Glucose, Calcium and Phosphate Levels | Potassium; Day 15; n= 17, 20, 18, 22, 20 | 0.03 Mmol/L | Standard Deviation 0.944 |
| Dapro 25 mg | Change From Baseline in Sodium, Potassium, Glucose, Calcium and Phosphate Levels | Sodium; Day 29; n= 17, 19, 18, 19, 17 | -0.5 Mmol/L | Standard Deviation 2.82 |
| Dapro 25 mg | Change From Baseline in Sodium, Potassium, Glucose, Calcium and Phosphate Levels | Phosphate; Day 15; n= 17, 20, 18, 22, 20 | 0.030 Mmol/L | Standard Deviation 0.3268 |
| Dapro 25 mg | Change From Baseline in Sodium, Potassium, Glucose, Calcium and Phosphate Levels | Phosphate; Day 29; n= 17, 19, 18, 19, 17 | 0.129 Mmol/L | Standard Deviation 0.274 |
| Dapro 25 mg | Change From Baseline in Sodium, Potassium, Glucose, Calcium and Phosphate Levels | Sodium; Day 43; n= 15, 20, 18, 21, 21 | -0.5 Mmol/L | Standard Deviation 2.6 |
| Dapro 25 mg | Change From Baseline in Sodium, Potassium, Glucose, Calcium and Phosphate Levels | Phosphate; Day 43; n= 15, 20, 18, 21, 21 | 0.102 Mmol/L | Standard Deviation 0.3433 |
| Dapro 25 mg | Change From Baseline in Sodium, Potassium, Glucose, Calcium and Phosphate Levels | Potassium; Day 43; n= 15, 20, 18, 21, 21 | -0.06 Mmol/L | Standard Deviation 0.579 |
| Dapro 25 mg | Change From Baseline in Sodium, Potassium, Glucose, Calcium and Phosphate Levels | Glucose; Day 15; n= 17, 20, 18, 22, 20 | 0.21 Mmol/L | Standard Deviation 1.62 |
| Dapro 25 mg | Change From Baseline in Sodium, Potassium, Glucose, Calcium and Phosphate Levels | Sodium; Day 15; n= 17, 20, 18, 22, 20 | -1.4 Mmol/L | Standard Deviation 2.06 |
| Dapro 30 mg | Change From Baseline in Sodium, Potassium, Glucose, Calcium and Phosphate Levels | Phosphate; Day 29; n= 17, 19, 18, 19, 17 | -0.026 Mmol/L | Standard Deviation 0.3653 |
| Dapro 30 mg | Change From Baseline in Sodium, Potassium, Glucose, Calcium and Phosphate Levels | Calcium; Day 15; n= 17, 20, 18, 22, 20 | -0.010 Mmol/L | Standard Deviation 0.0912 |
| Dapro 30 mg | Change From Baseline in Sodium, Potassium, Glucose, Calcium and Phosphate Levels | Glucose; Day 15; n= 17, 20, 18, 22, 20 | -0.03 Mmol/L | Standard Deviation 2.364 |
| Dapro 30 mg | Change From Baseline in Sodium, Potassium, Glucose, Calcium and Phosphate Levels | Sodium; Day 43; n= 15, 20, 18, 21, 21 | -0.6 Mmol/L | Standard Deviation 2.23 |
| Dapro 30 mg | Change From Baseline in Sodium, Potassium, Glucose, Calcium and Phosphate Levels | Sodium; Day 15; n= 17, 20, 18, 22, 20 | -1.0 Mmol/L | Standard Deviation 2.13 |
| Dapro 30 mg | Change From Baseline in Sodium, Potassium, Glucose, Calcium and Phosphate Levels | Potassium; Day 43; n= 15, 20, 18, 21, 21 | -0.02 Mmol/L | Standard Deviation 0.932 |
| Dapro 30 mg | Change From Baseline in Sodium, Potassium, Glucose, Calcium and Phosphate Levels | Glucose; Day 29; n= 17, 19, 18, 19, 17 | -0.36 Mmol/L | Standard Deviation 3.786 |
| Dapro 30 mg | Change From Baseline in Sodium, Potassium, Glucose, Calcium and Phosphate Levels | Phosphate; Day 43; n= 15, 20, 18, 21, 21 | -0.117 Mmol/L | Standard Deviation 0.5117 |
| Dapro 30 mg | Change From Baseline in Sodium, Potassium, Glucose, Calcium and Phosphate Levels | Calcium; Day 43; n= 15, 20, 18, 21, 21 | 0.033 Mmol/L | Standard Deviation 0.1489 |
| Dapro 30 mg | Change From Baseline in Sodium, Potassium, Glucose, Calcium and Phosphate Levels | Glucose; Day 43; n= 15, 20, 18, 21, 21 | -0.12 Mmol/L | Standard Deviation 3.619 |
| Dapro 30 mg | Change From Baseline in Sodium, Potassium, Glucose, Calcium and Phosphate Levels | Phosphate; Day 15; n= 17, 20, 18, 22, 20 | 0.095 Mmol/L | Standard Deviation 0.3367 |
| Dapro 30 mg | Change From Baseline in Sodium, Potassium, Glucose, Calcium and Phosphate Levels | Potassium; Day 15; n= 17, 20, 18, 22, 20 | -0.08 Mmol/L | Standard Deviation 0.635 |
| Dapro 30 mg | Change From Baseline in Sodium, Potassium, Glucose, Calcium and Phosphate Levels | Sodium; Day 29; n= 17, 19, 18, 19, 17 | -1.2 Mmol/L | Standard Deviation 2.7 |
| Dapro 30 mg | Change From Baseline in Sodium, Potassium, Glucose, Calcium and Phosphate Levels | Calcium; Day 29; n= 17, 19, 18, 19, 17 | 0.001 Mmol/L | Standard Deviation 0.1019 |
| Dapro 30 mg | Change From Baseline in Sodium, Potassium, Glucose, Calcium and Phosphate Levels | Potassium; Day 29; n= 17, 19, 18, 19, 17 | 0.11 Mmol/L | Standard Deviation 0.673 |
Secondary
Change From Baseline in Weight at Post-dialysis
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Weight at Post-dialysis | Day 15; n= 17, 20, 18, 22, 21 | -0.16 kg | Standard Deviation 0.634 |
| Placebo | Change From Baseline in Weight at Post-dialysis | Day 29; n= 17, 19, 18, 19, 17 | -0.11 kg | Standard Deviation 1.053 |
| Placebo | Change From Baseline in Weight at Post-dialysis | Day 43; n= 16, 20, 19, 21, 21 | -0.21 kg | Standard Deviation 0.665 |
| Dapro 10 mg | Change From Baseline in Weight at Post-dialysis | Day 29; n= 17, 19, 18, 19, 17 | -0.05 kg | Standard Deviation 1.583 |
| Dapro 10 mg | Change From Baseline in Weight at Post-dialysis | Day 15; n= 17, 20, 18, 22, 21 | 0.16 kg | Standard Deviation 0.971 |
| Dapro 10 mg | Change From Baseline in Weight at Post-dialysis | Day 43; n= 16, 20, 19, 21, 21 | 0.37 kg | Standard Deviation 2.76 |
| Dapro 15 mg | Change From Baseline in Weight at Post-dialysis | Day 43; n= 16, 20, 19, 21, 21 | -1.39 kg | Standard Deviation 5.759 |
| Dapro 15 mg | Change From Baseline in Weight at Post-dialysis | Day 15; n= 17, 20, 18, 22, 21 | -0.01 kg | Standard Deviation 0.617 |
| Dapro 15 mg | Change From Baseline in Weight at Post-dialysis | Day 29; n= 17, 19, 18, 19, 17 | -1.23 kg | Standard Deviation 5.913 |
| Dapro 25 mg | Change From Baseline in Weight at Post-dialysis | Day 43; n= 16, 20, 19, 21, 21 | 0.15 kg | Standard Deviation 1.472 |
| Dapro 25 mg | Change From Baseline in Weight at Post-dialysis | Day 15; n= 17, 20, 18, 22, 21 | 0.06 kg | Standard Deviation 0.799 |
| Dapro 25 mg | Change From Baseline in Weight at Post-dialysis | Day 29; n= 17, 19, 18, 19, 17 | -0.16 kg | Standard Deviation 1.046 |
| Dapro 30 mg | Change From Baseline in Weight at Post-dialysis | Day 15; n= 17, 20, 18, 22, 21 | -0.31 kg | Standard Deviation 1.215 |
| Dapro 30 mg | Change From Baseline in Weight at Post-dialysis | Day 29; n= 17, 19, 18, 19, 17 | -0.19 kg | Standard Deviation 1.244 |
| Dapro 30 mg | Change From Baseline in Weight at Post-dialysis | Day 43; n= 16, 20, 19, 21, 21 | 0.33 kg | Standard Deviation 2.169 |
Secondary
Erythrocyte Distribution Width Levels in Blood at Indicated Time Points
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Erythrocyte Distribution Width Levels in Blood at Indicated Time Points | Day 1; n= 18, 19, 20, 20, 21 | 15.13 Percentage of width | Standard Deviation 2.607 |
| Placebo | Erythrocyte Distribution Width Levels in Blood at Indicated Time Points | Day 15; n= 17, 19, 17, 21, 21 | 15.05 Percentage of width | Standard Deviation 2.088 |
| Placebo | Erythrocyte Distribution Width Levels in Blood at Indicated Time Points | Day 29; n= 16, 19, 17, 18, 17 | 15.15 Percentage of width | Standard Deviation 2.53 |
| Placebo | Erythrocyte Distribution Width Levels in Blood at Indicated Time Points | Day 43; n= 16, 20, 19, 21, 20 | 15.53 Percentage of width | Standard Deviation 2.866 |
| Dapro 10 mg | Erythrocyte Distribution Width Levels in Blood at Indicated Time Points | Day 1; n= 18, 19, 20, 20, 21 | 16.40 Percentage of width | Standard Deviation 2.082 |
| Dapro 10 mg | Erythrocyte Distribution Width Levels in Blood at Indicated Time Points | Day 43; n= 16, 20, 19, 21, 20 | 15.53 Percentage of width | Standard Deviation 2.018 |
| Dapro 10 mg | Erythrocyte Distribution Width Levels in Blood at Indicated Time Points | Day 15; n= 17, 19, 17, 21, 21 | 15.77 Percentage of width | Standard Deviation 1.569 |
| Dapro 10 mg | Erythrocyte Distribution Width Levels in Blood at Indicated Time Points | Day 29; n= 16, 19, 17, 18, 17 | 15.69 Percentage of width | Standard Deviation 1.75 |
| Dapro 15 mg | Erythrocyte Distribution Width Levels in Blood at Indicated Time Points | Day 43; n= 16, 20, 19, 21, 20 | 14.95 Percentage of width | Standard Deviation 1.269 |
| Dapro 15 mg | Erythrocyte Distribution Width Levels in Blood at Indicated Time Points | Day 15; n= 17, 19, 17, 21, 21 | 15.26 Percentage of width | Standard Deviation 1.197 |
| Dapro 15 mg | Erythrocyte Distribution Width Levels in Blood at Indicated Time Points | Day 29; n= 16, 19, 17, 18, 17 | 15.36 Percentage of width | Standard Deviation 1.287 |
| Dapro 15 mg | Erythrocyte Distribution Width Levels in Blood at Indicated Time Points | Day 1; n= 18, 19, 20, 20, 21 | 15.41 Percentage of width | Standard Deviation 1.627 |
| Dapro 25 mg | Erythrocyte Distribution Width Levels in Blood at Indicated Time Points | Day 1; n= 18, 19, 20, 20, 21 | 15.81 Percentage of width | Standard Deviation 2.504 |
| Dapro 25 mg | Erythrocyte Distribution Width Levels in Blood at Indicated Time Points | Day 15; n= 17, 19, 17, 21, 21 | 16.30 Percentage of width | Standard Deviation 2.331 |
| Dapro 25 mg | Erythrocyte Distribution Width Levels in Blood at Indicated Time Points | Day 43; n= 16, 20, 19, 21, 20 | 15.61 Percentage of width | Standard Deviation 1.297 |
| Dapro 25 mg | Erythrocyte Distribution Width Levels in Blood at Indicated Time Points | Day 29; n= 16, 19, 17, 18, 17 | 15.76 Percentage of width | Standard Deviation 1.253 |
| Dapro 30 mg | Erythrocyte Distribution Width Levels in Blood at Indicated Time Points | Day 43; n= 16, 20, 19, 21, 20 | 15.48 Percentage of width | Standard Deviation 1.389 |
| Dapro 30 mg | Erythrocyte Distribution Width Levels in Blood at Indicated Time Points | Day 29; n= 16, 19, 17, 18, 17 | 16.23 Percentage of width | Standard Deviation 1.668 |
| Dapro 30 mg | Erythrocyte Distribution Width Levels in Blood at Indicated Time Points | Day 15; n= 17, 19, 17, 21, 21 | 16.74 Percentage of width | Standard Deviation 1.912 |
| Dapro 30 mg | Erythrocyte Distribution Width Levels in Blood at Indicated Time Points | Day 1; n= 18, 19, 20, 20, 21 | 15.68 Percentage of width | Standard Deviation 1.725 |
Secondary
Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Neutrophils; Day 15; n= 17, 19, 17, 21, 21 | 4.666 10^12 cells/L | Standard Deviation 1.8113 |
| Placebo | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Leukocytes; Day 1; n= 18, 19, 19, 20, 21 | 6.28 10^12 cells/L | Standard Deviation 1.75 |
| Placebo | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Basophils; Day 43; n= 16, 20, 19, 19, 19 | 0.028 10^12 cells/L | Standard Deviation 0.0217 |
| Placebo | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Basophils; Day 29; n= 16, 18, 17, 17, 15 | 0.035 10^12 cells/L | Standard Deviation 0.0462 |
| Placebo | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Basophils; Day 15; n= 17, 19, 17, 21, 21 | 0.027 10^12 cells/L | Standard Deviation 0.0214 |
| Placebo | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Neutrophils; Day 29; n= 16, 18, 17, 17, 15 | 4.123 10^12 cells/L | Standard Deviation 1.2229 |
| Placebo | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Basophils; Day 1; n= 18, 19, 19, 20, 21 | 0.018 10^12 cells/L | Standard Deviation 0.0131 |
| Placebo | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Neutrophils; Day 43; n= 16, 20, 19, 19, 19 | 4.687 10^12 cells/L | Standard Deviation 1.8919 |
| Placebo | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Platelet; Day 29; n= 16, 19, 17, 17, 17 | 198.1 10^12 cells/L | Standard Deviation 76.39 |
| Placebo | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Monocytes; Day 43; n= 16, 20, 19, 19, 19 | 0.461 10^12 cells/L | Standard Deviation 0.1878 |
| Placebo | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Monocytes; Day 29; n= 16, 18, 17, 17, 15 | 0.444 10^12 cells/L | Standard Deviation 0.2076 |
| Placebo | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Monocytes; Day 15; n= 17, 19, 17, 21, 21 | 0.420 10^12 cells/L | Standard Deviation 0.2243 |
| Placebo | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Leukocytes; Day 15; n= 17, 19, 17, 21, 21 | 7.01 10^12 cells/L | Standard Deviation 2.14 |
| Placebo | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Platelet; Day 15; n= 17, 18, 17, 20, 21 | 205.4 10^12 cells/L | Standard Deviation 63 |
| Placebo | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Monocytes; Day 1; n= 18, 19, 20, 20, 21 | 0.401 10^12 cells/L | Standard Deviation 0.1511 |
| Placebo | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Lymphocytes; Day 43; n= 16, 20, 19, 19, 19 | 1.648 10^12 cells/L | Standard Deviation 0.5294 |
| Placebo | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Lymphocytes; Day 29; n= 16, 18, 17, 17, 15 | 1.870 10^12 cells/L | Standard Deviation 0.7427 |
| Placebo | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Leukocytes; Day 29; n= 16, 19, 17, 18, 17 | 6.66 10^12 cells/L | Standard Deviation 1.707 |
| Placebo | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Eosinophils; Day 29; n= 16, 18, 17, 17, 15 | 0.176 10^12 cells/L | Standard Deviation 0.1917 |
| Placebo | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Lymphocytes; Day 15; n= 17, 19, 17, 21, 21 | 1.735 10^12 cells/L | Standard Deviation 0.6699 |
| Placebo | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Lymphocytes; Day 1; n= 18, 19, 19, 20, 21 | 1.631 10^12 cells/L | Standard Deviation 0.4264 |
| Placebo | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Eosinophils; Day 43; n= 16, 20, 19, 19, 19 | 0.216 10^12 cells/L | Standard Deviation 0.2458 |
| Placebo | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Leukocytes; Day 43; n= 16, 20, 19, 20, 19 | 7.05 10^12 cells/L | Standard Deviation 2.006 |
| Placebo | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Platelet; Day 43; n= 15, 20, 19, 21, 20 | 220.8 10^12 cells/L | Standard Deviation 61.57 |
| Placebo | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Eosinophils; Day 15; n= 17, 19, 17, 21, 21 | 0.161 10^12 cells/L | Standard Deviation 0.1245 |
| Placebo | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Neutrophils; Day 1; n= 18, 19, 19, 20, 21 | 4.030 10^12 cells/L | Standard Deviation 1.6128 |
| Placebo | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Platelet; Day 1; n= 16, 19, 20, 19, 21 | 219.0 10^12 cells/L | Standard Deviation 65.04 |
| Placebo | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Eosinophils; Day 1; n= 18, 19, 19, 20, 21 | 0.189 10^12 cells/L | Standard Deviation 0.1946 |
| Dapro 10 mg | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Neutrophils; Day 29; n= 16, 18, 17, 17, 15 | 4.591 10^12 cells/L | Standard Deviation 1.9586 |
| Dapro 10 mg | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Lymphocytes; Day 15; n= 17, 19, 17, 21, 21 | 1.416 10^12 cells/L | Standard Deviation 0.567 |
| Dapro 10 mg | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Leukocytes; Day 1; n= 18, 19, 19, 20, 21 | 6.07 10^12 cells/L | Standard Deviation 1.601 |
| Dapro 10 mg | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Leukocytes; Day 15; n= 17, 19, 17, 21, 21 | 5.85 10^12 cells/L | Standard Deviation 1.72 |
| Dapro 10 mg | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Leukocytes; Day 29; n= 16, 19, 17, 18, 17 | 6.59 10^12 cells/L | Standard Deviation 1.89 |
| Dapro 10 mg | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Leukocytes; Day 43; n= 16, 20, 19, 20, 19 | 7.25 10^12 cells/L | Standard Deviation 2.52 |
| Dapro 10 mg | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Neutrophils; Day 1; n= 18, 19, 19, 20, 21 | 4.097 10^12 cells/L | Standard Deviation 1.5763 |
| Dapro 10 mg | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Neutrophils; Day 15; n= 17, 19, 17, 21, 21 | 3.887 10^12 cells/L | Standard Deviation 1.5659 |
| Dapro 10 mg | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Neutrophils; Day 43; n= 16, 20, 19, 19, 19 | 5.049 10^12 cells/L | Standard Deviation 2.3848 |
| Dapro 10 mg | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Basophils; Day 1; n= 18, 19, 19, 20, 21 | 0.016 10^12 cells/L | Standard Deviation 0.0134 |
| Dapro 10 mg | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Basophils; Day 15; n= 17, 19, 17, 21, 21 | 0.026 10^12 cells/L | Standard Deviation 0.0161 |
| Dapro 10 mg | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Basophils; Day 29; n= 16, 18, 17, 17, 15 | 0.021 10^12 cells/L | Standard Deviation 0.0128 |
| Dapro 10 mg | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Basophils; Day 43; n= 16, 20, 19, 19, 19 | 0.018 10^12 cells/L | Standard Deviation 0.0136 |
| Dapro 10 mg | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Eosinophils; Day 1; n= 18, 19, 19, 20, 21 | 0.174 10^12 cells/L | Standard Deviation 0.1593 |
| Dapro 10 mg | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Eosinophils; Day 15; n= 17, 19, 17, 21, 21 | 0.166 10^12 cells/L | Standard Deviation 0.1804 |
| Dapro 10 mg | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Eosinophils; Day 29; n= 16, 18, 17, 17, 15 | 0.149 10^12 cells/L | Standard Deviation 0.095 |
| Dapro 10 mg | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Eosinophils; Day 43; n= 16, 20, 19, 19, 19 | 0.210 10^12 cells/L | Standard Deviation 0.1969 |
| Dapro 10 mg | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Lymphocytes; Day 1; n= 18, 19, 19, 20, 21 | 1.393 10^12 cells/L | Standard Deviation 0.4587 |
| Dapro 10 mg | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Lymphocytes; Day 29; n= 16, 18, 17, 17, 15 | 1.427 10^12 cells/L | Standard Deviation 0.4187 |
| Dapro 10 mg | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Lymphocytes; Day 43; n= 16, 20, 19, 19, 19 | 1.509 10^12 cells/L | Standard Deviation 0.4386 |
| Dapro 10 mg | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Monocytes; Day 1; n= 18, 19, 20, 20, 21 | 0.396 10^12 cells/L | Standard Deviation 0.1591 |
| Dapro 10 mg | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Monocytes; Day 15; n= 17, 19, 17, 21, 21 | 0.352 10^12 cells/L | Standard Deviation 0.1457 |
| Dapro 10 mg | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Monocytes; Day 29; n= 16, 18, 17, 17, 15 | 0.457 10^12 cells/L | Standard Deviation 0.1503 |
| Dapro 10 mg | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Monocytes; Day 43; n= 16, 20, 19, 19, 19 | 0.459 10^12 cells/L | Standard Deviation 0.1916 |
| Dapro 10 mg | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Platelet; Day 1; n= 16, 19, 20, 19, 21 | 189.9 10^12 cells/L | Standard Deviation 36.7 |
| Dapro 10 mg | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Platelet; Day 15; n= 17, 18, 17, 20, 21 | 175.4 10^12 cells/L | Standard Deviation 44.08 |
| Dapro 10 mg | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Platelet; Day 29; n= 16, 19, 17, 17, 17 | 174.7 10^12 cells/L | Standard Deviation 52.5 |
| Dapro 10 mg | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Platelet; Day 43; n= 15, 20, 19, 21, 20 | 195.8 10^12 cells/L | Standard Deviation 68.33 |
| Dapro 15 mg | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Lymphocytes; Day 1; n= 18, 19, 19, 20, 21 | 1.739 10^12 cells/L | Standard Deviation 0.6964 |
| Dapro 15 mg | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Basophils; Day 1; n= 18, 19, 19, 20, 21 | 0.025 10^12 cells/L | Standard Deviation 0.0174 |
| Dapro 15 mg | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Monocytes; Day 15; n= 17, 19, 17, 21, 21 | 0.436 10^12 cells/L | Standard Deviation 0.2402 |
| Dapro 15 mg | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Leukocytes; Day 29; n= 16, 19, 17, 18, 17 | 5.88 10^12 cells/L | Standard Deviation 1.685 |
| Dapro 15 mg | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Eosinophils; Day 1; n= 18, 19, 19, 20, 21 | 0.184 10^12 cells/L | Standard Deviation 0.1696 |
| Dapro 15 mg | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Monocytes; Day 1; n= 18, 19, 20, 20, 21 | 0.435 10^12 cells/L | Standard Deviation 0.2703 |
| Dapro 15 mg | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Platelet; Day 29; n= 16, 19, 17, 17, 17 | 187.5 10^12 cells/L | Standard Deviation 62.66 |
| Dapro 15 mg | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Neutrophils; Day 15; n= 17, 19, 17, 21, 21 | 3.707 10^12 cells/L | Standard Deviation 1.6592 |
| Dapro 15 mg | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Lymphocytes; Day 29; n= 16, 18, 17, 17, 15 | 1.775 10^12 cells/L | Standard Deviation 0.6767 |
| Dapro 15 mg | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Neutrophils; Day 43; n= 16, 20, 19, 19, 19 | 3.545 10^12 cells/L | Standard Deviation 1.4027 |
| Dapro 15 mg | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Leukocytes; Day 15; n= 17, 19, 17, 21, 21 | 6.21 10^12 cells/L | Standard Deviation 1.918 |
| Dapro 15 mg | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Leukocytes; Day 43; n= 16, 20, 19, 20, 19 | 6.00 10^12 cells/L | Standard Deviation 1.694 |
| Dapro 15 mg | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Platelet; Day 43; n= 15, 20, 19, 21, 20 | 188.6 10^12 cells/L | Standard Deviation 69.28 |
| Dapro 15 mg | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Lymphocytes; Day 43; n= 16, 20, 19, 19, 19 | 1.736 10^12 cells/L | Standard Deviation 0.3916 |
| Dapro 15 mg | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Eosinophils; Day 15; n= 17, 19, 17, 21, 21 | 0.192 10^12 cells/L | Standard Deviation 0.2355 |
| Dapro 15 mg | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Basophils; Day 15; n= 17, 19, 17, 21, 21 | 0.022 10^12 cells/L | Standard Deviation 0.0139 |
| Dapro 15 mg | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Lymphocytes; Day 15; n= 17, 19, 17, 21, 21 | 1.842 10^12 cells/L | Standard Deviation 0.7381 |
| Dapro 15 mg | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Platelet; Day 15; n= 17, 18, 17, 20, 21 | 198.5 10^12 cells/L | Standard Deviation 73.65 |
| Dapro 15 mg | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Eosinophils; Day 29; n= 16, 18, 17, 17, 15 | 0.145 10^12 cells/L | Standard Deviation 0.1136 |
| Dapro 15 mg | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Basophils; Day 43; n= 16, 20, 19, 19, 19 | 0.020 10^12 cells/L | Standard Deviation 0.0183 |
| Dapro 15 mg | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Neutrophils; Day 29; n= 16, 18, 17, 17, 15 | 3.522 10^12 cells/L | Standard Deviation 1.4546 |
| Dapro 15 mg | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Monocytes; Day 43; n= 16, 20, 19, 19, 19 | 0.461 10^12 cells/L | Standard Deviation 0.2614 |
| Dapro 15 mg | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Basophils; Day 29; n= 16, 18, 17, 17, 15 | 0.021 10^12 cells/L | Standard Deviation 0.015 |
| Dapro 15 mg | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Eosinophils; Day 43; n= 16, 20, 19, 19, 19 | 0.232 10^12 cells/L | Standard Deviation 0.2727 |
| Dapro 15 mg | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Platelet; Day 1; n= 16, 19, 20, 19, 21 | 198.0 10^12 cells/L | Standard Deviation 71.03 |
| Dapro 15 mg | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Leukocytes; Day 1; n= 18, 19, 19, 20, 21 | 5.88 10^12 cells/L | Standard Deviation 1.51 |
| Dapro 15 mg | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Neutrophils; Day 1; n= 18, 19, 19, 20, 21 | 3.522 10^12 cells/L | Standard Deviation 1.3492 |
| Dapro 15 mg | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Monocytes; Day 29; n= 16, 18, 17, 17, 15 | 0.403 10^12 cells/L | Standard Deviation 0.1385 |
| Dapro 25 mg | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Monocytes; Day 15; n= 17, 19, 17, 21, 21 | 0.446 10^12 cells/L | Standard Deviation 0.2085 |
| Dapro 25 mg | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Basophils; Day 43; n= 16, 20, 19, 19, 19 | 0.025 10^12 cells/L | Standard Deviation 0.0204 |
| Dapro 25 mg | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Eosinophils; Day 1; n= 18, 19, 19, 20, 21 | 0.196 10^12 cells/L | Standard Deviation 0.231 |
| Dapro 25 mg | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Eosinophils; Day 15; n= 17, 19, 17, 21, 21 | 0.187 10^12 cells/L | Standard Deviation 0.2186 |
| Dapro 25 mg | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Eosinophils; Day 29; n= 16, 18, 17, 17, 15 | 0.237 10^12 cells/L | Standard Deviation 0.2785 |
| Dapro 25 mg | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Platelet; Day 15; n= 17, 18, 17, 20, 21 | 194.8 10^12 cells/L | Standard Deviation 49.08 |
| Dapro 25 mg | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Eosinophils; Day 43; n= 16, 20, 19, 19, 19 | 0.243 10^12 cells/L | Standard Deviation 0.267 |
| Dapro 25 mg | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Leukocytes; Day 29; n= 16, 19, 17, 18, 17 | 6.33 10^12 cells/L | Standard Deviation 1.82 |
| Dapro 25 mg | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Lymphocytes; Day 1; n= 18, 19, 19, 20, 21 | 1.747 10^12 cells/L | Standard Deviation 0.7325 |
| Dapro 25 mg | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Lymphocytes; Day 15; n= 17, 19, 17, 21, 21 | 1.526 10^12 cells/L | Standard Deviation 0.6697 |
| Dapro 25 mg | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Neutrophils; Day 1; n= 18, 19, 19, 20, 21 | 3.954 10^12 cells/L | Standard Deviation 1.4097 |
| Dapro 25 mg | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Lymphocytes; Day 29; n= 16, 18, 17, 17, 15 | 1.612 10^12 cells/L | Standard Deviation 0.5775 |
| Dapro 25 mg | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Leukocytes; Day 15; n= 17, 19, 17, 21, 21 | 6.52 10^12 cells/L | Standard Deviation 1.427 |
| Dapro 25 mg | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Platelet; Day 43; n= 15, 20, 19, 21, 20 | 194.1 10^12 cells/L | Standard Deviation 50.35 |
| Dapro 25 mg | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Lymphocytes; Day 43; n= 16, 20, 19, 19, 19 | 1.721 10^12 cells/L | Standard Deviation 0.6644 |
| Dapro 25 mg | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Monocytes; Day 1; n= 18, 19, 20, 20, 21 | 0.518 10^12 cells/L | Standard Deviation 0.2077 |
| Dapro 25 mg | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Platelet; Day 29; n= 16, 19, 17, 17, 17 | 198.9 10^12 cells/L | Standard Deviation 55.07 |
| Dapro 25 mg | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Basophils; Day 29; n= 16, 18, 17, 17, 15 | 0.024 10^12 cells/L | Standard Deviation 0.0111 |
| Dapro 25 mg | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Leukocytes; Day 1; n= 18, 19, 19, 20, 21 | 6.44 10^12 cells/L | Standard Deviation 1.595 |
| Dapro 25 mg | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Monocytes; Day 29; n= 16, 18, 17, 17, 15 | 0.600 10^12 cells/L | Standard Deviation 0.3465 |
| Dapro 25 mg | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Monocytes; Day 43; n= 16, 20, 19, 19, 19 | 0.513 10^12 cells/L | Standard Deviation 0.2739 |
| Dapro 25 mg | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Neutrophils; Day 29; n= 16, 18, 17, 17, 15 | 3.978 10^12 cells/L | Standard Deviation 1.7026 |
| Dapro 25 mg | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Neutrophils; Day 43; n= 16, 20, 19, 19, 19 | 4.477 10^12 cells/L | Standard Deviation 2.248 |
| Dapro 25 mg | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Leukocytes; Day 43; n= 16, 20, 19, 20, 19 | 6.77 10^12 cells/L | Standard Deviation 2.547 |
| Dapro 25 mg | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Basophils; Day 1; n= 18, 19, 19, 20, 21 | 0.028 10^12 cells/L | Standard Deviation 0.0204 |
| Dapro 25 mg | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Basophils; Day 15; n= 17, 19, 17, 21, 21 | 0.025 10^12 cells/L | Standard Deviation 0.0325 |
| Dapro 25 mg | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Neutrophils; Day 15; n= 17, 19, 17, 21, 21 | 4.346 10^12 cells/L | Standard Deviation 1.224 |
| Dapro 25 mg | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Platelet; Day 1; n= 16, 19, 20, 19, 21 | 196.0 10^12 cells/L | Standard Deviation 61.12 |
| Dapro 30 mg | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Platelet; Day 15; n= 17, 18, 17, 20, 21 | 181.5 10^12 cells/L | Standard Deviation 66.59 |
| Dapro 30 mg | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Basophils; Day 1; n= 18, 19, 19, 20, 21 | 0.017 10^12 cells/L | Standard Deviation 0.0142 |
| Dapro 30 mg | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Monocytes; Day 29; n= 16, 18, 17, 17, 15 | 0.426 10^12 cells/L | Standard Deviation 0.2628 |
| Dapro 30 mg | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Eosinophils; Day 43; n= 16, 20, 19, 19, 19 | 0.217 10^12 cells/L | Standard Deviation 0.1899 |
| Dapro 30 mg | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Leukocytes; Day 43; n= 16, 20, 19, 20, 19 | 6.42 10^12 cells/L | Standard Deviation 2.01 |
| Dapro 30 mg | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Leukocytes; Day 29; n= 16, 19, 17, 18, 17 | 6.11 10^12 cells/L | Standard Deviation 2.574 |
| Dapro 30 mg | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Neutrophils; Day 15; n= 17, 19, 17, 21, 21 | 4.129 10^12 cells/L | Standard Deviation 1.6604 |
| Dapro 30 mg | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Monocytes; Day 43; n= 16, 20, 19, 19, 19 | 0.429 10^12 cells/L | Standard Deviation 0.2047 |
| Dapro 30 mg | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Basophils; Day 43; n= 16, 20, 19, 19, 19 | 0.024 10^12 cells/L | Standard Deviation 0.013 |
| Dapro 30 mg | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Neutrophils; Day 29; n= 16, 18, 17, 17, 15 | 4.224 10^12 cells/L | Standard Deviation 2.2017 |
| Dapro 30 mg | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Eosinophils; Day 29; n= 16, 18, 17, 17, 15 | 0.185 10^12 cells/L | Standard Deviation 0.0798 |
| Dapro 30 mg | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Eosinophils; Day 15; n= 17, 19, 17, 21, 21 | 0.186 10^12 cells/L | Standard Deviation 0.1914 |
| Dapro 30 mg | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Eosinophils; Day 1; n= 18, 19, 19, 20, 21 | 0.240 10^12 cells/L | Standard Deviation 0.2115 |
| Dapro 30 mg | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Platelet; Day 1; n= 16, 19, 20, 19, 21 | 192.3 10^12 cells/L | Standard Deviation 70.85 |
| Dapro 30 mg | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Neutrophils; Day 43; n= 16, 20, 19, 19, 19 | 4.343 10^12 cells/L | Standard Deviation 1.6235 |
| Dapro 30 mg | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Lymphocytes; Day 43; n= 16, 20, 19, 19, 19 | 1.399 10^12 cells/L | Standard Deviation 0.5562 |
| Dapro 30 mg | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Lymphocytes; Day 29; n= 16, 18, 17, 17, 15 | 1.181 10^12 cells/L | Standard Deviation 0.3418 |
| Dapro 30 mg | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Leukocytes; Day 15; n= 17, 19, 17, 21, 21 | 5.87 10^12 cells/L | Standard Deviation 1.961 |
| Dapro 30 mg | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Lymphocytes; Day 15; n= 17, 19, 17, 21, 21 | 1.206 10^12 cells/L | Standard Deviation 0.4609 |
| Dapro 30 mg | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Basophils; Day 29; n= 16, 18, 17, 17, 15 | 0.027 10^12 cells/L | Standard Deviation 0.0315 |
| Dapro 30 mg | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Monocytes; Day 1; n= 18, 19, 20, 20, 21 | 0.421 10^12 cells/L | Standard Deviation 0.1722 |
| Dapro 30 mg | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Leukocytes; Day 1; n= 18, 19, 19, 20, 21 | 5.90 10^12 cells/L | Standard Deviation 1.825 |
| Dapro 30 mg | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Platelet; Day 43; n= 15, 20, 19, 21, 20 | 170.0 10^12 cells/L | Standard Deviation 44.61 |
| Dapro 30 mg | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Lymphocytes; Day 1; n= 18, 19, 19, 20, 21 | 1.442 10^12 cells/L | Standard Deviation 0.4998 |
| Dapro 30 mg | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Neutrophils; Day 1; n= 18, 19, 19, 20, 21 | 3.785 10^12 cells/L | Standard Deviation 1.5024 |
| Dapro 30 mg | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Monocytes; Day 15; n= 17, 19, 17, 21, 21 | 0.384 10^12 cells/L | Standard Deviation 0.216 |
| Dapro 30 mg | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Basophils; Day 15; n= 17, 19, 17, 21, 21 | 0.024 10^12 cells/L | Standard Deviation 0.014 |
| Dapro 30 mg | Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points | Platelet; Day 29; n= 16, 19, 17, 17, 17 | 194.8 10^12 cells/L | Standard Deviation 81.57 |
Secondary
Maximum Observed Change From Baseline in Plasma Erythropoietin (EPO)
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
Population: ITT Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Maximum Observed Change From Baseline in Plasma Erythropoietin (EPO) | 53.761 International unit per liter (IU/L) | Standard Deviation 132.6875 |
| Dapro 10 mg | Maximum Observed Change From Baseline in Plasma Erythropoietin (EPO) | 2.255 International unit per liter (IU/L) | Standard Deviation 84.8921 |
| Dapro 15 mg | Maximum Observed Change From Baseline in Plasma Erythropoietin (EPO) | 73.369 International unit per liter (IU/L) | Standard Deviation 95.9772 |
| Dapro 25 mg | Maximum Observed Change From Baseline in Plasma Erythropoietin (EPO) | 302.529 International unit per liter (IU/L) | Standard Deviation 469.8312 |
| Dapro 30 mg | Maximum Observed Change From Baseline in Plasma Erythropoietin (EPO) | 477.644 International unit per liter (IU/L) | Standard Deviation 388.9757 |
Secondary
Maximum Observed Concentration of Dapro in Plasma (Cmax)
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
Population: PK Population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Maximum Observed Concentration of Dapro in Plasma (Cmax) | 140.0 ng/mL | Geometric Coefficient of Variation 104 |
| Dapro 10 mg | Maximum Observed Concentration of Dapro in Plasma (Cmax) | 141.4 ng/mL | Geometric Coefficient of Variation 248.8 |
| Dapro 15 mg | Maximum Observed Concentration of Dapro in Plasma (Cmax) | 246.9 ng/mL | Geometric Coefficient of Variation 311.5 |
| Dapro 25 mg | Maximum Observed Concentration of Dapro in Plasma (Cmax) | 387.3 ng/mL | Geometric Coefficient of Variation 99.4 |
Secondary
Maximum Observed Percent Change From Baseline in Vascular Endothelial Growth Factor (VEGF)
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
Population: ITT Population
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Placebo | Maximum Observed Percent Change From Baseline in Vascular Endothelial Growth Factor (VEGF) | 20.35 Nanograms per liter (ng/L) |
| Dapro 10 mg | Maximum Observed Percent Change From Baseline in Vascular Endothelial Growth Factor (VEGF) | 43.75 Nanograms per liter (ng/L) |
| Dapro 15 mg | Maximum Observed Percent Change From Baseline in Vascular Endothelial Growth Factor (VEGF) | 32.16 Nanograms per liter (ng/L) |
| Dapro 25 mg | Maximum Observed Percent Change From Baseline in Vascular Endothelial Growth Factor (VEGF) | 53.34 Nanograms per liter (ng/L) |
| Dapro 30 mg | Maximum Observed Percent Change From Baseline in Vascular Endothelial Growth Factor (VEGF) | 76.09 Nanograms per liter (ng/L) |
Secondary
Mean Corpuscular Hemoglobin Concentration (MCHC) Levels in Blood at Indicated Time Points
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean Corpuscular Hemoglobin Concentration (MCHC) Levels in Blood at Indicated Time Points | Day 1; n= 18, 19, 20, 20, 21 | 322.9 g/L | Standard Deviation 13.39 |
| Placebo | Mean Corpuscular Hemoglobin Concentration (MCHC) Levels in Blood at Indicated Time Points | Day 15; n= 17, 19, 17, 21, 21 | 321.5 g/L | Standard Deviation 11.22 |
| Placebo | Mean Corpuscular Hemoglobin Concentration (MCHC) Levels in Blood at Indicated Time Points | Day 29; n= 16, 19, 17, 18, 17 | 323.3 g/L | Standard Deviation 14.9 |
| Placebo | Mean Corpuscular Hemoglobin Concentration (MCHC) Levels in Blood at Indicated Time Points | Day 43; n= 16, 20, 19, 21, 20 | 321.9 g/L | Standard Deviation 13.22 |
| Dapro 10 mg | Mean Corpuscular Hemoglobin Concentration (MCHC) Levels in Blood at Indicated Time Points | Day 1; n= 18, 19, 20, 20, 21 | 321.7 g/L | Standard Deviation 12.61 |
| Dapro 10 mg | Mean Corpuscular Hemoglobin Concentration (MCHC) Levels in Blood at Indicated Time Points | Day 43; n= 16, 20, 19, 21, 20 | 325.2 g/L | Standard Deviation 11.98 |
| Dapro 10 mg | Mean Corpuscular Hemoglobin Concentration (MCHC) Levels in Blood at Indicated Time Points | Day 15; n= 17, 19, 17, 21, 21 | 324.0 g/L | Standard Deviation 7.79 |
| Dapro 10 mg | Mean Corpuscular Hemoglobin Concentration (MCHC) Levels in Blood at Indicated Time Points | Day 29; n= 16, 19, 17, 18, 17 | 329.6 g/L | Standard Deviation 12.61 |
| Dapro 15 mg | Mean Corpuscular Hemoglobin Concentration (MCHC) Levels in Blood at Indicated Time Points | Day 43; n= 16, 20, 19, 21, 20 | 325.5 g/L | Standard Deviation 11.23 |
| Dapro 15 mg | Mean Corpuscular Hemoglobin Concentration (MCHC) Levels in Blood at Indicated Time Points | Day 15; n= 17, 19, 17, 21, 21 | 324.8 g/L | Standard Deviation 8.35 |
| Dapro 15 mg | Mean Corpuscular Hemoglobin Concentration (MCHC) Levels in Blood at Indicated Time Points | Day 29; n= 16, 19, 17, 18, 17 | 325.4 g/L | Standard Deviation 10.25 |
| Dapro 15 mg | Mean Corpuscular Hemoglobin Concentration (MCHC) Levels in Blood at Indicated Time Points | Day 1; n= 18, 19, 20, 20, 21 | 319.5 g/L | Standard Deviation 15.36 |
| Dapro 25 mg | Mean Corpuscular Hemoglobin Concentration (MCHC) Levels in Blood at Indicated Time Points | Day 1; n= 18, 19, 20, 20, 21 | 321.5 g/L | Standard Deviation 12.91 |
| Dapro 25 mg | Mean Corpuscular Hemoglobin Concentration (MCHC) Levels in Blood at Indicated Time Points | Day 15; n= 17, 19, 17, 21, 21 | 318.3 g/L | Standard Deviation 12.06 |
| Dapro 25 mg | Mean Corpuscular Hemoglobin Concentration (MCHC) Levels in Blood at Indicated Time Points | Day 43; n= 16, 20, 19, 21, 20 | 321.0 g/L | Standard Deviation 11 |
| Dapro 25 mg | Mean Corpuscular Hemoglobin Concentration (MCHC) Levels in Blood at Indicated Time Points | Day 29; n= 16, 19, 17, 18, 17 | 323.6 g/L | Standard Deviation 8.61 |
| Dapro 30 mg | Mean Corpuscular Hemoglobin Concentration (MCHC) Levels in Blood at Indicated Time Points | Day 43; n= 16, 20, 19, 21, 20 | 327.0 g/L | Standard Deviation 10.66 |
| Dapro 30 mg | Mean Corpuscular Hemoglobin Concentration (MCHC) Levels in Blood at Indicated Time Points | Day 29; n= 16, 19, 17, 18, 17 | 323.9 g/L | Standard Deviation 11.73 |
| Dapro 30 mg | Mean Corpuscular Hemoglobin Concentration (MCHC) Levels in Blood at Indicated Time Points | Day 15; n= 17, 19, 17, 21, 21 | 322.7 g/L | Standard Deviation 14.75 |
| Dapro 30 mg | Mean Corpuscular Hemoglobin Concentration (MCHC) Levels in Blood at Indicated Time Points | Day 1; n= 18, 19, 20, 20, 21 | 327.6 g/L | Standard Deviation 12.65 |
Secondary
Mean Corpuscular Hemoglobin (MCH) Levels in Blood at Indicated Time Points
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean Corpuscular Hemoglobin (MCH) Levels in Blood at Indicated Time Points | Day 1; n= 18, 19, 20, 20, 21 | 31.19 Pg | Standard Deviation 2.538 |
| Placebo | Mean Corpuscular Hemoglobin (MCH) Levels in Blood at Indicated Time Points | Day 15; n= 17, 19, 17, 21, 21 | 30.83 Pg | Standard Deviation 2.1 |
| Placebo | Mean Corpuscular Hemoglobin (MCH) Levels in Blood at Indicated Time Points | Day 29; n= 16, 19, 17, 18, 17 | 30.97 Pg | Standard Deviation 2.29 |
| Placebo | Mean Corpuscular Hemoglobin (MCH) Levels in Blood at Indicated Time Points | Day 43; n= 16, 20, 19, 21, 20 | 30.86 Pg | Standard Deviation 1.992 |
| Dapro 10 mg | Mean Corpuscular Hemoglobin (MCH) Levels in Blood at Indicated Time Points | Day 1; n= 18, 19, 20, 20, 21 | 30.95 Pg | Standard Deviation 1.889 |
| Dapro 10 mg | Mean Corpuscular Hemoglobin (MCH) Levels in Blood at Indicated Time Points | Day 43; n= 16, 20, 19, 21, 20 | 31.04 Pg | Standard Deviation 1.87 |
| Dapro 10 mg | Mean Corpuscular Hemoglobin (MCH) Levels in Blood at Indicated Time Points | Day 15; n= 17, 19, 17, 21, 21 | 2.100 Pg | Standard Deviation 1.866 |
| Dapro 10 mg | Mean Corpuscular Hemoglobin (MCH) Levels in Blood at Indicated Time Points | Day 29; n= 16, 19, 17, 18, 17 | 31.60 Pg | Standard Deviation 2.194 |
| Dapro 15 mg | Mean Corpuscular Hemoglobin (MCH) Levels in Blood at Indicated Time Points | Day 43; n= 16, 20, 19, 21, 20 | 30.49 Pg | Standard Deviation 2.155 |
| Dapro 15 mg | Mean Corpuscular Hemoglobin (MCH) Levels in Blood at Indicated Time Points | Day 15; n= 17, 19, 17, 21, 21 | 30.74 Pg | Standard Deviation 1.476 |
| Dapro 15 mg | Mean Corpuscular Hemoglobin (MCH) Levels in Blood at Indicated Time Points | Day 29; n= 16, 19, 17, 18, 17 | 30.56 Pg | Standard Deviation 2.236 |
| Dapro 15 mg | Mean Corpuscular Hemoglobin (MCH) Levels in Blood at Indicated Time Points | Day 1; n= 18, 19, 20, 20, 21 | 30.19 Pg | Standard Deviation 2.145 |
| Dapro 25 mg | Mean Corpuscular Hemoglobin (MCH) Levels in Blood at Indicated Time Points | Day 1; n= 18, 19, 20, 20, 21 | 30.70 Pg | Standard Deviation 1.781 |
| Dapro 25 mg | Mean Corpuscular Hemoglobin (MCH) Levels in Blood at Indicated Time Points | Day 15; n= 17, 19, 17, 21, 21 | 30.85 Pg | Standard Deviation 1.619 |
| Dapro 25 mg | Mean Corpuscular Hemoglobin (MCH) Levels in Blood at Indicated Time Points | Day 43; n= 16, 20, 19, 21, 20 | 30.67 Pg | Standard Deviation 1.846 |
| Dapro 25 mg | Mean Corpuscular Hemoglobin (MCH) Levels in Blood at Indicated Time Points | Day 29; n= 16, 19, 17, 18, 17 | 31.16 Pg | Standard Deviation 1.729 |
| Dapro 30 mg | Mean Corpuscular Hemoglobin (MCH) Levels in Blood at Indicated Time Points | Day 43; n= 16, 20, 19, 21, 20 | 31.84 Pg | Standard Deviation 2.143 |
| Dapro 30 mg | Mean Corpuscular Hemoglobin (MCH) Levels in Blood at Indicated Time Points | Day 29; n= 16, 19, 17, 18, 17 | 31.68 Pg | Standard Deviation 2.224 |
| Dapro 30 mg | Mean Corpuscular Hemoglobin (MCH) Levels in Blood at Indicated Time Points | Day 15; n= 17, 19, 17, 21, 21 | 31.70 Pg | Standard Deviation 2.315 |
| Dapro 30 mg | Mean Corpuscular Hemoglobin (MCH) Levels in Blood at Indicated Time Points | Day 1; n= 18, 19, 20, 20, 21 | 31.46 Pg | Standard Deviation 1.942 |
Secondary
Mean Corpuscular Volume (MCV) Levels in Blood at Indicated Time Points
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean Corpuscular Volume (MCV) Levels in Blood at Indicated Time Points | Day 1; n= 18, 19, 20, 20, 21 | 96.7 Femtoliter (fL) | Standard Deviation 5.94 |
| Placebo | Mean Corpuscular Volume (MCV) Levels in Blood at Indicated Time Points | Day 15; n= 17, 19, 17, 21, 21 | 95.9 Femtoliter (fL) | Standard Deviation 6.02 |
| Placebo | Mean Corpuscular Volume (MCV) Levels in Blood at Indicated Time Points | Day 29; n= 16, 19, 17, 18, 17 | 95.8 Femtoliter (fL) | Standard Deviation 5.83 |
| Placebo | Mean Corpuscular Volume (MCV) Levels in Blood at Indicated Time Points | Day 43; n= 16, 20, 19, 21, 20 | 96.1 Femtoliter (fL) | Standard Deviation 5.91 |
| Dapro 10 mg | Mean Corpuscular Volume (MCV) Levels in Blood at Indicated Time Points | Day 1; n= 18, 19, 20, 20, 21 | 96.4 Femtoliter (fL) | Standard Deviation 5.68 |
| Dapro 10 mg | Mean Corpuscular Volume (MCV) Levels in Blood at Indicated Time Points | Day 43; n= 16, 20, 19, 21, 20 | 95.4 Femtoliter (fL) | Standard Deviation 5.08 |
| Dapro 10 mg | Mean Corpuscular Volume (MCV) Levels in Blood at Indicated Time Points | Day 15; n= 17, 19, 17, 21, 21 | 95.8 Femtoliter (fL) | Standard Deviation 6.27 |
| Dapro 10 mg | Mean Corpuscular Volume (MCV) Levels in Blood at Indicated Time Points | Day 29; n= 16, 19, 17, 18, 17 | 95.9 Femtoliter (fL) | Standard Deviation 6.05 |
| Dapro 15 mg | Mean Corpuscular Volume (MCV) Levels in Blood at Indicated Time Points | Day 43; n= 16, 20, 19, 21, 20 | 93.7 Femtoliter (fL) | Standard Deviation 6.09 |
| Dapro 15 mg | Mean Corpuscular Volume (MCV) Levels in Blood at Indicated Time Points | Day 15; n= 17, 19, 17, 21, 21 | 94.8 Femtoliter (fL) | Standard Deviation 4.53 |
| Dapro 15 mg | Mean Corpuscular Volume (MCV) Levels in Blood at Indicated Time Points | Day 29; n= 16, 19, 17, 18, 17 | 94.1 Femtoliter (fL) | Standard Deviation 5.94 |
| Dapro 15 mg | Mean Corpuscular Volume (MCV) Levels in Blood at Indicated Time Points | Day 1; n= 18, 19, 20, 20, 21 | 94.7 Femtoliter (fL) | Standard Deviation 5.28 |
| Dapro 25 mg | Mean Corpuscular Volume (MCV) Levels in Blood at Indicated Time Points | Day 1; n= 18, 19, 20, 20, 21 | 95.7 Femtoliter (fL) | Standard Deviation 4.91 |
| Dapro 25 mg | Mean Corpuscular Volume (MCV) Levels in Blood at Indicated Time Points | Day 15; n= 17, 19, 17, 21, 21 | 97.0 Femtoliter (fL) | Standard Deviation 6.41 |
| Dapro 25 mg | Mean Corpuscular Volume (MCV) Levels in Blood at Indicated Time Points | Day 43; n= 16, 20, 19, 21, 20 | 95.6 Femtoliter (fL) | Standard Deviation 5.27 |
| Dapro 25 mg | Mean Corpuscular Volume (MCV) Levels in Blood at Indicated Time Points | Day 29; n= 16, 19, 17, 18, 17 | 96.3 Femtoliter (fL) | Standard Deviation 4.76 |
| Dapro 30 mg | Mean Corpuscular Volume (MCV) Levels in Blood at Indicated Time Points | Day 43; n= 16, 20, 19, 21, 20 | 97.5 Femtoliter (fL) | Standard Deviation 5.98 |
| Dapro 30 mg | Mean Corpuscular Volume (MCV) Levels in Blood at Indicated Time Points | Day 29; n= 16, 19, 17, 18, 17 | 97.8 Femtoliter (fL) | Standard Deviation 4.96 |
| Dapro 30 mg | Mean Corpuscular Volume (MCV) Levels in Blood at Indicated Time Points | Day 15; n= 17, 19, 17, 21, 21 | 98.3 Femtoliter (fL) | Standard Deviation 5.57 |
| Dapro 30 mg | Mean Corpuscular Volume (MCV) Levels in Blood at Indicated Time Points | Day 1; n= 18, 19, 20, 20, 21 | 96.1 Femtoliter (fL) | Standard Deviation 5.61 |
Secondary
Number of Participants Who Discontinued Study Treatment
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
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants Who Discontinued Study Treatment | Physician decision | 1 Participants |
| Placebo | Number of Participants Who Discontinued Study Treatment | AEs | 0 Participants |
| Placebo | Number of Participants Who Discontinued Study Treatment | Withdrawal by subject | 1 Participants |
| Placebo | Number of Participants Who Discontinued Study Treatment | Protocol deviation | 1 Participants |
| Placebo | Number of Participants Who Discontinued Study Treatment | Participant reached stopping criteria | 0 Participants |
| Dapro 10 mg | Number of Participants Who Discontinued Study Treatment | Physician decision | 0 Participants |
| Dapro 10 mg | Number of Participants Who Discontinued Study Treatment | Participant reached stopping criteria | 1 Participants |
| Dapro 10 mg | Number of Participants Who Discontinued Study Treatment | Protocol deviation | 0 Participants |
| Dapro 10 mg | Number of Participants Who Discontinued Study Treatment | Withdrawal by subject | 0 Participants |
| Dapro 10 mg | Number of Participants Who Discontinued Study Treatment | AEs | 0 Participants |
| Dapro 15 mg | Number of Participants Who Discontinued Study Treatment | Participant reached stopping criteria | 2 Participants |
| Dapro 15 mg | Number of Participants Who Discontinued Study Treatment | AEs | 1 Participants |
| Dapro 15 mg | Number of Participants Who Discontinued Study Treatment | Protocol deviation | 0 Participants |
| Dapro 15 mg | Number of Participants Who Discontinued Study Treatment | Physician decision | 0 Participants |
| Dapro 15 mg | Number of Participants Who Discontinued Study Treatment | Withdrawal by subject | 1 Participants |
| Dapro 25 mg | Number of Participants Who Discontinued Study Treatment | Withdrawal by subject | 0 Participants |
| Dapro 25 mg | Number of Participants Who Discontinued Study Treatment | AEs | 0 Participants |
| Dapro 25 mg | Number of Participants Who Discontinued Study Treatment | Physician decision | 0 Participants |
| Dapro 25 mg | Number of Participants Who Discontinued Study Treatment | Participant reached stopping criteria | 3 Participants |
| Dapro 25 mg | Number of Participants Who Discontinued Study Treatment | Protocol deviation | 1 Participants |
| Dapro 30 mg | Number of Participants Who Discontinued Study Treatment | Participant reached stopping criteria | 4 Participants |
| Dapro 30 mg | Number of Participants Who Discontinued Study Treatment | Physician decision | 0 Participants |
| Dapro 30 mg | Number of Participants Who Discontinued Study Treatment | AEs | 1 Participants |
| Dapro 30 mg | Number of Participants Who Discontinued Study Treatment | Withdrawal by subject | 0 Participants |
| Dapro 30 mg | Number of Participants Who Discontinued Study Treatment | Protocol deviation | 2 Participants |
Secondary
Number of Participants With Abnormal Electrocardiogram (ECG) Findings at Indicated Time Points
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
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With Abnormal Electrocardiogram (ECG) Findings at Indicated Time Points | Day 29; Abnormal; NCS; n=17,19,18,19,17 | 12 Participants |
| Placebo | Number of Participants With Abnormal Electrocardiogram (ECG) Findings at Indicated Time Points | Baseline(Week -4);Abnormal; NCS;n=19,20,20,22,22 | 10 Participants |
| Placebo | Number of Participants With Abnormal Electrocardiogram (ECG) Findings at Indicated Time Points | Baseline(Week-4);Abnormal;CS;n=19,20,20,22,22 | 0 Participants |
| Placebo | Number of Participants With Abnormal Electrocardiogram (ECG) Findings at Indicated Time Points | Day 29; Abnormal; CS; n=17,19,18,19,17 | 0 Participants |
| Dapro 10 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings at Indicated Time Points | Baseline(Week-4);Abnormal;CS;n=19,20,20,22,22 | 0 Participants |
| Dapro 10 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings at Indicated Time Points | Baseline(Week -4);Abnormal; NCS;n=19,20,20,22,22 | 15 Participants |
| Dapro 10 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings at Indicated Time Points | Day 29; Abnormal; CS; n=17,19,18,19,17 | 0 Participants |
| Dapro 10 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings at Indicated Time Points | Day 29; Abnormal; NCS; n=17,19,18,19,17 | 14 Participants |
| Dapro 15 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings at Indicated Time Points | Baseline(Week -4);Abnormal; NCS;n=19,20,20,22,22 | 18 Participants |
| Dapro 15 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings at Indicated Time Points | Day 29; Abnormal; CS; n=17,19,18,19,17 | 0 Participants |
| Dapro 15 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings at Indicated Time Points | Baseline(Week-4);Abnormal;CS;n=19,20,20,22,22 | 0 Participants |
| Dapro 15 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings at Indicated Time Points | Day 29; Abnormal; NCS; n=17,19,18,19,17 | 16 Participants |
| Dapro 25 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings at Indicated Time Points | Baseline(Week -4);Abnormal; NCS;n=19,20,20,22,22 | 12 Participants |
| Dapro 25 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings at Indicated Time Points | Day 29; Abnormal; CS; n=17,19,18,19,17 | 1 Participants |
| Dapro 25 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings at Indicated Time Points | Day 29; Abnormal; NCS; n=17,19,18,19,17 | 8 Participants |
| Dapro 25 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings at Indicated Time Points | Baseline(Week-4);Abnormal;CS;n=19,20,20,22,22 | 1 Participants |
| Dapro 30 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings at Indicated Time Points | Day 29; Abnormal; CS; n=17,19,18,19,17 | 0 Participants |
| Dapro 30 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings at Indicated Time Points | Baseline(Week -4);Abnormal; NCS;n=19,20,20,22,22 | 16 Participants |
| Dapro 30 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings at Indicated Time Points | Baseline(Week-4);Abnormal;CS;n=19,20,20,22,22 | 0 Participants |
| Dapro 30 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings at Indicated Time Points | Day 29; Abnormal; NCS; n=17,19,18,19,17 | 12 Participants |
Secondary
Number of Participants With AEs and Serious Adverse Events (SAEs)
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
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With AEs and Serious Adverse Events (SAEs) | Any AE | 10 Participants |
| Placebo | Number of Participants With AEs and Serious Adverse Events (SAEs) | Any SAE | 4 Participants |
| Dapro 10 mg | Number of Participants With AEs and Serious Adverse Events (SAEs) | Any AE | 10 Participants |
| Dapro 10 mg | Number of Participants With AEs and Serious Adverse Events (SAEs) | Any SAE | 3 Participants |
| Dapro 15 mg | Number of Participants With AEs and Serious Adverse Events (SAEs) | Any AE | 6 Participants |
| Dapro 15 mg | Number of Participants With AEs and Serious Adverse Events (SAEs) | Any SAE | 2 Participants |
| Dapro 25 mg | Number of Participants With AEs and Serious Adverse Events (SAEs) | Any SAE | 1 Participants |
| Dapro 25 mg | Number of Participants With AEs and Serious Adverse Events (SAEs) | Any AE | 7 Participants |
| Dapro 30 mg | Number of Participants With AEs and Serious Adverse Events (SAEs) | Any AE | 7 Participants |
| Dapro 30 mg | Number of Participants With AEs and Serious Adverse Events (SAEs) | Any SAE | 3 Participants |
Secondary
Percent Change From Baseline in Hepcidin at 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.
Time frame: Baseline and Day 29
Population: ITT Population
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Placebo | Percent Change From Baseline in Hepcidin at Day 29 | 27.81 Micrograms per liter (µg/L) |
| Dapro 10 mg | Percent Change From Baseline in Hepcidin at Day 29 | 35.37 Micrograms per liter (µg/L) |
| Dapro 15 mg | Percent Change From Baseline in Hepcidin at Day 29 | 3.83 Micrograms per liter (µg/L) |
| Dapro 25 mg | Percent Change From Baseline in Hepcidin at Day 29 | -36.74 Micrograms per liter (µg/L) |
| Dapro 30 mg | Percent Change From Baseline in Hepcidin at Day 29 | -36.09 Micrograms per liter (µg/L) |
Secondary
Pulse Rate Values at Pre-dialysis and Post-dialysis
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Pulse Rate Values at Pre-dialysis and Post-dialysis | Post-dialysis; Day 29; n= 17, 19, 18, 19, 17 | 73.6 Beats per minute | Standard Deviation 7.1 |
| Placebo | Pulse Rate Values at Pre-dialysis and Post-dialysis | Post-dialysis; Day 43; n= 16, 20, 19, 21, 21 | 72.0 Beats per minute | Standard Deviation 12.04 |
| Placebo | Pulse Rate Values at Pre-dialysis and Post-dialysis | Post-dialysis; Day 15; n= 17, 20, 18, 22, 21 | 72.5 Beats per minute | Standard Deviation 12.69 |
| Placebo | Pulse Rate Values at Pre-dialysis and Post-dialysis | Pre-dialysis; Day 1; n= 19, 20, 20, 22, 22 | 68.5 Beats per minute | Standard Deviation 7.95 |
| Placebo | Pulse Rate Values at Pre-dialysis and Post-dialysis | Pre-dialysis; Day 29; n= 17, 19, 18, 19, 17 | 70.4 Beats per minute | Standard Deviation 8.31 |
| Placebo | Pulse Rate Values at Pre-dialysis and Post-dialysis | Post-dialysis; Day 1; n= 19, 20, 20, 22, 22 | 71.0 Beats per minute | Standard Deviation 11.54 |
| Placebo | Pulse Rate Values at Pre-dialysis and Post-dialysis | Pre-dialysis; Day 43; n= 16, 20, 19, 21, 21 | 71.5 Beats per minute | Standard Deviation 9.17 |
| Placebo | Pulse Rate Values at Pre-dialysis and Post-dialysis | Pre-dialysis; Day 15; n= 17, 20, 18, 22, 21 | 76.1 Beats per minute | Standard Deviation 10.31 |
| Dapro 10 mg | Pulse Rate Values at Pre-dialysis and Post-dialysis | Post-dialysis; Day 1; n= 19, 20, 20, 22, 22 | 68.7 Beats per minute | Standard Deviation 11.19 |
| Dapro 10 mg | Pulse Rate Values at Pre-dialysis and Post-dialysis | Post-dialysis; Day 15; n= 17, 20, 18, 22, 21 | 67.7 Beats per minute | Standard Deviation 12.24 |
| Dapro 10 mg | Pulse Rate Values at Pre-dialysis and Post-dialysis | Pre-dialysis; Day 15; n= 17, 20, 18, 22, 21 | 67.3 Beats per minute | Standard Deviation 9.2 |
| Dapro 10 mg | Pulse Rate Values at Pre-dialysis and Post-dialysis | Pre-dialysis; Day 1; n= 19, 20, 20, 22, 22 | 69.9 Beats per minute | Standard Deviation 9.18 |
| Dapro 10 mg | Pulse Rate Values at Pre-dialysis and Post-dialysis | Post-dialysis; Day 43; n= 16, 20, 19, 21, 21 | 69.1 Beats per minute | Standard Deviation 10.21 |
| Dapro 10 mg | Pulse Rate Values at Pre-dialysis and Post-dialysis | Pre-dialysis; Day 29; n= 17, 19, 18, 19, 17 | 70.3 Beats per minute | Standard Deviation 11.54 |
| Dapro 10 mg | Pulse Rate Values at Pre-dialysis and Post-dialysis | Pre-dialysis; Day 43; n= 16, 20, 19, 21, 21 | 69.9 Beats per minute | Standard Deviation 9.34 |
| Dapro 10 mg | Pulse Rate Values at Pre-dialysis and Post-dialysis | Post-dialysis; Day 29; n= 17, 19, 18, 19, 17 | 69.9 Beats per minute | Standard Deviation 9.6 |
| Dapro 15 mg | Pulse Rate Values at Pre-dialysis and Post-dialysis | Pre-dialysis; Day 15; n= 17, 20, 18, 22, 21 | 68.3 Beats per minute | Standard Deviation 7.51 |
| Dapro 15 mg | Pulse Rate Values at Pre-dialysis and Post-dialysis | Post-dialysis; Day 43; n= 16, 20, 19, 21, 21 | 68.0 Beats per minute | Standard Deviation 10.28 |
| Dapro 15 mg | Pulse Rate Values at Pre-dialysis and Post-dialysis | Post-dialysis; Day 15; n= 17, 20, 18, 22, 21 | 70.1 Beats per minute | Standard Deviation 12.49 |
| Dapro 15 mg | Pulse Rate Values at Pre-dialysis and Post-dialysis | Pre-dialysis; Day 43; n= 16, 20, 19, 21, 21 | 66.9 Beats per minute | Standard Deviation 6.74 |
| Dapro 15 mg | Pulse Rate Values at Pre-dialysis and Post-dialysis | Post-dialysis; Day 29; n= 17, 19, 18, 19, 17 | 68.8 Beats per minute | Standard Deviation 11.29 |
| Dapro 15 mg | Pulse Rate Values at Pre-dialysis and Post-dialysis | Post-dialysis; Day 1; n= 19, 20, 20, 22, 22 | 66.3 Beats per minute | Standard Deviation 8.37 |
| Dapro 15 mg | Pulse Rate Values at Pre-dialysis and Post-dialysis | Pre-dialysis; Day 29; n= 17, 19, 18, 19, 17 | 69.6 Beats per minute | Standard Deviation 9.53 |
| Dapro 15 mg | Pulse Rate Values at Pre-dialysis and Post-dialysis | Pre-dialysis; Day 1; n= 19, 20, 20, 22, 22 | 66.7 Beats per minute | Standard Deviation 7.01 |
| Dapro 25 mg | Pulse Rate Values at Pre-dialysis and Post-dialysis | Pre-dialysis; Day 43; n= 16, 20, 19, 21, 21 | 71.3 Beats per minute | Standard Deviation 10.08 |
| Dapro 25 mg | Pulse Rate Values at Pre-dialysis and Post-dialysis | Post-dialysis; Day 29; n= 17, 19, 18, 19, 17 | 72.2 Beats per minute | Standard Deviation 9.52 |
| Dapro 25 mg | Pulse Rate Values at Pre-dialysis and Post-dialysis | Pre-dialysis; Day 1; n= 19, 20, 20, 22, 22 | 71.4 Beats per minute | Standard Deviation 11.25 |
| Dapro 25 mg | Pulse Rate Values at Pre-dialysis and Post-dialysis | Pre-dialysis; Day 15; n= 17, 20, 18, 22, 21 | 72.1 Beats per minute | Standard Deviation 11.89 |
| Dapro 25 mg | Pulse Rate Values at Pre-dialysis and Post-dialysis | Pre-dialysis; Day 29; n= 17, 19, 18, 19, 17 | 70.8 Beats per minute | Standard Deviation 9.91 |
| Dapro 25 mg | Pulse Rate Values at Pre-dialysis and Post-dialysis | Post-dialysis; Day 1; n= 19, 20, 20, 22, 22 | 73.2 Beats per minute | Standard Deviation 12.77 |
| Dapro 25 mg | Pulse Rate Values at Pre-dialysis and Post-dialysis | Post-dialysis; Day 15; n= 17, 20, 18, 22, 21 | 73.0 Beats per minute | Standard Deviation 12.07 |
| Dapro 25 mg | Pulse Rate Values at Pre-dialysis and Post-dialysis | Post-dialysis; Day 43; n= 16, 20, 19, 21, 21 | 71.9 Beats per minute | Standard Deviation 11.02 |
| Dapro 30 mg | Pulse Rate Values at Pre-dialysis and Post-dialysis | Post-dialysis; Day 1; n= 19, 20, 20, 22, 22 | 78.8 Beats per minute | Standard Deviation 11.61 |
| Dapro 30 mg | Pulse Rate Values at Pre-dialysis and Post-dialysis | Pre-dialysis; Day 43; n= 16, 20, 19, 21, 21 | 75.8 Beats per minute | Standard Deviation 8.29 |
| Dapro 30 mg | Pulse Rate Values at Pre-dialysis and Post-dialysis | Post-dialysis; Day 29; n= 17, 19, 18, 19, 17 | 77.4 Beats per minute | Standard Deviation 10.04 |
| Dapro 30 mg | Pulse Rate Values at Pre-dialysis and Post-dialysis | Pre-dialysis; Day 29; n= 17, 19, 18, 19, 17 | 73.4 Beats per minute | Standard Deviation 11.45 |
| Dapro 30 mg | Pulse Rate Values at Pre-dialysis and Post-dialysis | Pre-dialysis; Day 15; n= 17, 20, 18, 22, 21 | 75.1 Beats per minute | Standard Deviation 12.68 |
| Dapro 30 mg | Pulse Rate Values at Pre-dialysis and Post-dialysis | Pre-dialysis; Day 1; n= 19, 20, 20, 22, 22 | 76.5 Beats per minute | Standard Deviation 9.35 |
| Dapro 30 mg | Pulse Rate Values at Pre-dialysis and Post-dialysis | Post-dialysis; Day 43; n= 16, 20, 19, 21, 21 | 77.3 Beats per minute | Standard Deviation 10.26 |
| Dapro 30 mg | Pulse Rate Values at Pre-dialysis and Post-dialysis | Post-dialysis; Day 15; n= 17, 20, 18, 22, 21 | 78.1 Beats per minute | Standard Deviation 15.72 |
Secondary
Sodium, Potassium, Glucose, Calcium, Phosphate Levels in Blood at Indicated Time Points
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Sodium, Potassium, Glucose, Calcium, Phosphate Levels in Blood at Indicated Time Points | Glucose; Day 29; n= 17, 19, 18, 19, 17 | 8.21 Millimoles per liter (mmol/L) | Standard Deviation 4.951 |
| Placebo | Sodium, Potassium, Glucose, Calcium, Phosphate Levels in Blood at Indicated Time Points | Phosphate; Day 1; n= 18, 20, 20, 22, 22 | 1.608 Millimoles per liter (mmol/L) | Standard Deviation 0.5143 |
| Placebo | Sodium, Potassium, Glucose, Calcium, Phosphate Levels in Blood at Indicated Time Points | Calcium corrected; Day 15; n= 17, 20, 18, 22, 20 | 2.261 Millimoles per liter (mmol/L) | Standard Deviation 0.1698 |
| Placebo | Sodium, Potassium, Glucose, Calcium, Phosphate Levels in Blood at Indicated Time Points | Potassium; Day 1; n= 18, 20, 20, 22, 22 | 4.68 Millimoles per liter (mmol/L) | Standard Deviation 0.84 |
| Placebo | Sodium, Potassium, Glucose, Calcium, Phosphate Levels in Blood at Indicated Time Points | Phosphate; Day 29; n= 17, 19, 18, 19, 17 | 1.709 Millimoles per liter (mmol/L) | Standard Deviation 0.5872 |
| Placebo | Sodium, Potassium, Glucose, Calcium, Phosphate Levels in Blood at Indicated Time Points | Calcium corrected; Day 43; n= 15, 20, 18, 21, 21 | 2.251 Millimoles per liter (mmol/L) | Standard Deviation 0.1582 |
| Placebo | Sodium, Potassium, Glucose, Calcium, Phosphate Levels in Blood at Indicated Time Points | Potassium; Day 15; n= 17, 20, 18, 22, 20 | 4.72 Millimoles per liter (mmol/L) | Standard Deviation 0.763 |
| Placebo | Sodium, Potassium, Glucose, Calcium, Phosphate Levels in Blood at Indicated Time Points | Glucose; Day 1; n= 18, 20, 20, 22, 22 | 6.66 Millimoles per liter (mmol/L) | Standard Deviation 3.088 |
| Placebo | Sodium, Potassium, Glucose, Calcium, Phosphate Levels in Blood at Indicated Time Points | Sodium; Day 29; n= 17, 19, 18, 19, 17 | 137.8 Millimoles per liter (mmol/L) | Standard Deviation 3.96 |
| Placebo | Sodium, Potassium, Glucose, Calcium, Phosphate Levels in Blood at Indicated Time Points | Glucose; Day 15; n= 17, 20, 18, 22, 20 | 7.89 Millimoles per liter (mmol/L) | Standard Deviation 3.425 |
| Placebo | Sodium, Potassium, Glucose, Calcium, Phosphate Levels in Blood at Indicated Time Points | Calcium corrected; Day 29; n= 17, 19, 18, 19, 17 | 2.205 Millimoles per liter (mmol/L) | Standard Deviation 0.1431 |
| Placebo | Sodium, Potassium, Glucose, Calcium, Phosphate Levels in Blood at Indicated Time Points | Potassium; Day 29; n= 17, 19, 18, 19, 17 | 4.78 Millimoles per liter (mmol/L) | Standard Deviation 0.919 |
| Placebo | Sodium, Potassium, Glucose, Calcium, Phosphate Levels in Blood at Indicated Time Points | Sodium; Day 1; n= 18, 20, 20, 22, 22 | 138.8 Millimoles per liter (mmol/L) | Standard Deviation 2.85 |
| Placebo | Sodium, Potassium, Glucose, Calcium, Phosphate Levels in Blood at Indicated Time Points | Phosphate; Day 43; n= 15, 20, 18, 21, 21 | 1.550 Millimoles per liter (mmol/L) | Standard Deviation 0.5828 |
| Placebo | Sodium, Potassium, Glucose, Calcium, Phosphate Levels in Blood at Indicated Time Points | Phosphate; Day 15; n= 17, 20, 18, 22, 20 | 1.621 Millimoles per liter (mmol/L) | Standard Deviation 0.4221 |
| Placebo | Sodium, Potassium, Glucose, Calcium, Phosphate Levels in Blood at Indicated Time Points | Sodium; Day 15; n= 17, 20, 18, 22, 20 | 137.7 Millimoles per liter (mmol/L) | Standard Deviation 3.16 |
| Placebo | Sodium, Potassium, Glucose, Calcium, Phosphate Levels in Blood at Indicated Time Points | Potassium; Day 43; n= 15, 20, 18, 21, 21 | 4.69 Millimoles per liter (mmol/L) | Standard Deviation 0.951 |
| Placebo | Sodium, Potassium, Glucose, Calcium, Phosphate Levels in Blood at Indicated Time Points | Sodium; Day 43; n= 15, 20, 18, 21, 21 | 139.2 Millimoles per liter (mmol/L) | Standard Deviation 2.88 |
| Placebo | Sodium, Potassium, Glucose, Calcium, Phosphate Levels in Blood at Indicated Time Points | Glucose; Day 43; n= 15, 20, 18, 21, 21 | 6.93 Millimoles per liter (mmol/L) | Standard Deviation 3.126 |
| Placebo | Sodium, Potassium, Glucose, Calcium, Phosphate Levels in Blood at Indicated Time Points | Calcium corrected; Day 1; n= 18, 20, 20, 22, 22 | 2.286 Millimoles per liter (mmol/L) | Standard Deviation 0.2116 |
| Dapro 10 mg | Sodium, Potassium, Glucose, Calcium, Phosphate Levels in Blood at Indicated Time Points | Sodium; Day 1; n= 18, 20, 20, 22, 22 | 138.1 Millimoles per liter (mmol/L) | Standard Deviation 2.31 |
| Dapro 10 mg | Sodium, Potassium, Glucose, Calcium, Phosphate Levels in Blood at Indicated Time Points | Glucose; Day 1; n= 18, 20, 20, 22, 22 | 6.66 Millimoles per liter (mmol/L) | Standard Deviation 2.716 |
| Dapro 10 mg | Sodium, Potassium, Glucose, Calcium, Phosphate Levels in Blood at Indicated Time Points | Glucose; Day 29; n= 17, 19, 18, 19, 17 | 7.49 Millimoles per liter (mmol/L) | Standard Deviation 3.949 |
| Dapro 10 mg | Sodium, Potassium, Glucose, Calcium, Phosphate Levels in Blood at Indicated Time Points | Glucose; Day 15; n= 17, 20, 18, 22, 20 | 7.16 Millimoles per liter (mmol/L) | Standard Deviation 2.844 |
| Dapro 10 mg | Sodium, Potassium, Glucose, Calcium, Phosphate Levels in Blood at Indicated Time Points | Sodium; Day 15; n= 17, 20, 18, 22, 20 | 137.5 Millimoles per liter (mmol/L) | Standard Deviation 2.72 |
| Dapro 10 mg | Sodium, Potassium, Glucose, Calcium, Phosphate Levels in Blood at Indicated Time Points | Phosphate; Day 15; n= 17, 20, 18, 22, 20 | 1.710 Millimoles per liter (mmol/L) | Standard Deviation 0.3912 |
| Dapro 10 mg | Sodium, Potassium, Glucose, Calcium, Phosphate Levels in Blood at Indicated Time Points | Sodium; Day 29; n= 17, 19, 18, 19, 17 | 136.8 Millimoles per liter (mmol/L) | Standard Deviation 2.7 |
| Dapro 10 mg | Sodium, Potassium, Glucose, Calcium, Phosphate Levels in Blood at Indicated Time Points | Phosphate; Day 1; n= 18, 20, 20, 22, 22 | 1.528 Millimoles per liter (mmol/L) | Standard Deviation 0.5557 |
| Dapro 10 mg | Sodium, Potassium, Glucose, Calcium, Phosphate Levels in Blood at Indicated Time Points | Sodium; Day 43; n= 15, 20, 18, 21, 21 | 138.1 Millimoles per liter (mmol/L) | Standard Deviation 1.77 |
| Dapro 10 mg | Sodium, Potassium, Glucose, Calcium, Phosphate Levels in Blood at Indicated Time Points | Glucose; Day 43; n= 15, 20, 18, 21, 21 | 6.72 Millimoles per liter (mmol/L) | Standard Deviation 2.965 |
| Dapro 10 mg | Sodium, Potassium, Glucose, Calcium, Phosphate Levels in Blood at Indicated Time Points | Calcium corrected; Day 43; n= 15, 20, 18, 21, 21 | 2.235 Millimoles per liter (mmol/L) | Standard Deviation 0.1593 |
| Dapro 10 mg | Sodium, Potassium, Glucose, Calcium, Phosphate Levels in Blood at Indicated Time Points | Potassium; Day 1; n= 18, 20, 20, 22, 22 | 4.73 Millimoles per liter (mmol/L) | Standard Deviation 0.768 |
| Dapro 10 mg | Sodium, Potassium, Glucose, Calcium, Phosphate Levels in Blood at Indicated Time Points | Potassium; Day 15; n= 17, 20, 18, 22, 20 | 4.77 Millimoles per liter (mmol/L) | Standard Deviation 0.542 |
| Dapro 10 mg | Sodium, Potassium, Glucose, Calcium, Phosphate Levels in Blood at Indicated Time Points | Phosphate; Day 43; n= 15, 20, 18, 21, 21 | 1.460 Millimoles per liter (mmol/L) | Standard Deviation 0.455 |
| Dapro 10 mg | Sodium, Potassium, Glucose, Calcium, Phosphate Levels in Blood at Indicated Time Points | Calcium corrected; Day 29; n= 17, 19, 18, 19, 17 | 2.248 Millimoles per liter (mmol/L) | Standard Deviation 0.1352 |
| Dapro 10 mg | Sodium, Potassium, Glucose, Calcium, Phosphate Levels in Blood at Indicated Time Points | Potassium; Day 29; n= 17, 19, 18, 19, 17 | 4.87 Millimoles per liter (mmol/L) | Standard Deviation 0.751 |
| Dapro 10 mg | Sodium, Potassium, Glucose, Calcium, Phosphate Levels in Blood at Indicated Time Points | Calcium corrected; Day 15; n= 17, 20, 18, 22, 20 | 2.219 Millimoles per liter (mmol/L) | Standard Deviation 0.1252 |
| Dapro 10 mg | Sodium, Potassium, Glucose, Calcium, Phosphate Levels in Blood at Indicated Time Points | Calcium corrected; Day 1; n= 18, 20, 20, 22, 22 | 2.270 Millimoles per liter (mmol/L) | Standard Deviation 0.1244 |
| Dapro 10 mg | Sodium, Potassium, Glucose, Calcium, Phosphate Levels in Blood at Indicated Time Points | Potassium; Day 43; n= 15, 20, 18, 21, 21 | 4.68 Millimoles per liter (mmol/L) | Standard Deviation 0.562 |
| Dapro 10 mg | Sodium, Potassium, Glucose, Calcium, Phosphate Levels in Blood at Indicated Time Points | Phosphate; Day 29; n= 17, 19, 18, 19, 17 | 1.592 Millimoles per liter (mmol/L) | Standard Deviation 0.4121 |
| Dapro 15 mg | Sodium, Potassium, Glucose, Calcium, Phosphate Levels in Blood at Indicated Time Points | Phosphate; Day 15; n= 17, 20, 18, 22, 20 | 1.642 Millimoles per liter (mmol/L) | Standard Deviation 0.5021 |
| Dapro 15 mg | Sodium, Potassium, Glucose, Calcium, Phosphate Levels in Blood at Indicated Time Points | Sodium; Day 1; n= 18, 20, 20, 22, 22 | 138.7 Millimoles per liter (mmol/L) | Standard Deviation 2.83 |
| Dapro 15 mg | Sodium, Potassium, Glucose, Calcium, Phosphate Levels in Blood at Indicated Time Points | Sodium; Day 15; n= 17, 20, 18, 22, 20 | 138.1 Millimoles per liter (mmol/L) | Standard Deviation 1.6 |
| Dapro 15 mg | Sodium, Potassium, Glucose, Calcium, Phosphate Levels in Blood at Indicated Time Points | Sodium; Day 29; n= 17, 19, 18, 19, 17 | 137.9 Millimoles per liter (mmol/L) | Standard Deviation 2.85 |
| Dapro 15 mg | Sodium, Potassium, Glucose, Calcium, Phosphate Levels in Blood at Indicated Time Points | Sodium; Day 43; n= 15, 20, 18, 21, 21 | 137.9 Millimoles per liter (mmol/L) | Standard Deviation 2.37 |
| Dapro 15 mg | Sodium, Potassium, Glucose, Calcium, Phosphate Levels in Blood at Indicated Time Points | Potassium; Day 15; n= 17, 20, 18, 22, 20 | 4.57 Millimoles per liter (mmol/L) | Standard Deviation 0.635 |
| Dapro 15 mg | Sodium, Potassium, Glucose, Calcium, Phosphate Levels in Blood at Indicated Time Points | Potassium; Day 29; n= 17, 19, 18, 19, 17 | 4.57 Millimoles per liter (mmol/L) | Standard Deviation 0.472 |
| Dapro 15 mg | Sodium, Potassium, Glucose, Calcium, Phosphate Levels in Blood at Indicated Time Points | Potassium; Day 43; n= 15, 20, 18, 21, 21 | 4.59 Millimoles per liter (mmol/L) | Standard Deviation 0.657 |
| Dapro 15 mg | Sodium, Potassium, Glucose, Calcium, Phosphate Levels in Blood at Indicated Time Points | Glucose; Day 1; n= 18, 20, 20, 22, 22 | 6.41 Millimoles per liter (mmol/L) | Standard Deviation 3.507 |
| Dapro 15 mg | Sodium, Potassium, Glucose, Calcium, Phosphate Levels in Blood at Indicated Time Points | Glucose; Day 15; n= 17, 20, 18, 22, 20 | 7.03 Millimoles per liter (mmol/L) | Standard Deviation 3.236 |
| Dapro 15 mg | Sodium, Potassium, Glucose, Calcium, Phosphate Levels in Blood at Indicated Time Points | Glucose; Day 29; n= 17, 19, 18, 19, 17 | 7.21 Millimoles per liter (mmol/L) | Standard Deviation 3.953 |
| Dapro 15 mg | Sodium, Potassium, Glucose, Calcium, Phosphate Levels in Blood at Indicated Time Points | Glucose; Day 43; n= 15, 20, 18, 21, 21 | 7.09 Millimoles per liter (mmol/L) | Standard Deviation 3.533 |
| Dapro 15 mg | Sodium, Potassium, Glucose, Calcium, Phosphate Levels in Blood at Indicated Time Points | Calcium corrected; Day 1; n= 18, 20, 20, 22, 22 | 2.241 Millimoles per liter (mmol/L) | Standard Deviation 0.1675 |
| Dapro 15 mg | Sodium, Potassium, Glucose, Calcium, Phosphate Levels in Blood at Indicated Time Points | Calcium corrected; Day 15; n= 17, 20, 18, 22, 20 | 2.213 Millimoles per liter (mmol/L) | Standard Deviation 0.1723 |
| Dapro 15 mg | Sodium, Potassium, Glucose, Calcium, Phosphate Levels in Blood at Indicated Time Points | Calcium corrected; Day 29; n= 17, 19, 18, 19, 17 | 2.244 Millimoles per liter (mmol/L) | Standard Deviation 0.1577 |
| Dapro 15 mg | Sodium, Potassium, Glucose, Calcium, Phosphate Levels in Blood at Indicated Time Points | Calcium corrected; Day 43; n= 15, 20, 18, 21, 21 | 2.271 Millimoles per liter (mmol/L) | Standard Deviation 0.1823 |
| Dapro 15 mg | Sodium, Potassium, Glucose, Calcium, Phosphate Levels in Blood at Indicated Time Points | Phosphate; Day 1; n= 18, 20, 20, 22, 22 | 1.498 Millimoles per liter (mmol/L) | Standard Deviation 0.5265 |
| Dapro 15 mg | Sodium, Potassium, Glucose, Calcium, Phosphate Levels in Blood at Indicated Time Points | Potassium; Day 1; n= 18, 20, 20, 22, 22 | 4.64 Millimoles per liter (mmol/L) | Standard Deviation 0.826 |
| Dapro 15 mg | Sodium, Potassium, Glucose, Calcium, Phosphate Levels in Blood at Indicated Time Points | Phosphate; Day 29; n= 17, 19, 18, 19, 17 | 1.644 Millimoles per liter (mmol/L) | Standard Deviation 0.5322 |
| Dapro 15 mg | Sodium, Potassium, Glucose, Calcium, Phosphate Levels in Blood at Indicated Time Points | Phosphate; Day 43; n= 15, 20, 18, 21, 21 | 1.472 Millimoles per liter (mmol/L) | Standard Deviation 0.424 |
| Dapro 25 mg | Sodium, Potassium, Glucose, Calcium, Phosphate Levels in Blood at Indicated Time Points | Glucose; Day 43; n= 15, 20, 18, 21, 21 | 6.27 Millimoles per liter (mmol/L) | Standard Deviation 1.958 |
| Dapro 25 mg | Sodium, Potassium, Glucose, Calcium, Phosphate Levels in Blood at Indicated Time Points | Potassium; Day 43; n= 15, 20, 18, 21, 21 | 4.76 Millimoles per liter (mmol/L) | Standard Deviation 0.752 |
| Dapro 25 mg | Sodium, Potassium, Glucose, Calcium, Phosphate Levels in Blood at Indicated Time Points | Phosphate; Day 43; n= 15, 20, 18, 21, 21 | 1.412 Millimoles per liter (mmol/L) | Standard Deviation 0.4441 |
| Dapro 25 mg | Sodium, Potassium, Glucose, Calcium, Phosphate Levels in Blood at Indicated Time Points | Calcium corrected; Day 1; n= 18, 20, 20, 22, 22 | 2.219 Millimoles per liter (mmol/L) | Standard Deviation 0.1589 |
| Dapro 25 mg | Sodium, Potassium, Glucose, Calcium, Phosphate Levels in Blood at Indicated Time Points | Potassium; Day 29; n= 17, 19, 18, 19, 17 | 4.86 Millimoles per liter (mmol/L) | Standard Deviation 0.619 |
| Dapro 25 mg | Sodium, Potassium, Glucose, Calcium, Phosphate Levels in Blood at Indicated Time Points | Phosphate; Day 29; n= 17, 19, 18, 19, 17 | 1.453 Millimoles per liter (mmol/L) | Standard Deviation 0.4489 |
| Dapro 25 mg | Sodium, Potassium, Glucose, Calcium, Phosphate Levels in Blood at Indicated Time Points | Calcium corrected; Day 15; n= 17, 20, 18, 22, 20 | 2.188 Millimoles per liter (mmol/L) | Standard Deviation 0.136 |
| Dapro 25 mg | Sodium, Potassium, Glucose, Calcium, Phosphate Levels in Blood at Indicated Time Points | Potassium; Day 15; n= 17, 20, 18, 22, 20 | 4.82 Millimoles per liter (mmol/L) | Standard Deviation 0.765 |
| Dapro 25 mg | Sodium, Potassium, Glucose, Calcium, Phosphate Levels in Blood at Indicated Time Points | Calcium corrected; Day 29; n= 17, 19, 18, 19, 17 | 2.198 Millimoles per liter (mmol/L) | Standard Deviation 0.1343 |
| Dapro 25 mg | Sodium, Potassium, Glucose, Calcium, Phosphate Levels in Blood at Indicated Time Points | Sodium; Day 1; n= 18, 20, 20, 22, 22 | 139.4 Millimoles per liter (mmol/L) | Standard Deviation 2.38 |
| Dapro 25 mg | Sodium, Potassium, Glucose, Calcium, Phosphate Levels in Blood at Indicated Time Points | Calcium corrected; Day 43; n= 15, 20, 18, 21, 21 | 2.201 Millimoles per liter (mmol/L) | Standard Deviation 0.1206 |
| Dapro 25 mg | Sodium, Potassium, Glucose, Calcium, Phosphate Levels in Blood at Indicated Time Points | Sodium; Day 43; n= 15, 20, 18, 21, 21 | 138.8 Millimoles per liter (mmol/L) | Standard Deviation 2.02 |
| Dapro 25 mg | Sodium, Potassium, Glucose, Calcium, Phosphate Levels in Blood at Indicated Time Points | Potassium; Day 1; n= 18, 20, 20, 22, 22 | 4.79 Millimoles per liter (mmol/L) | Standard Deviation 0.514 |
| Dapro 25 mg | Sodium, Potassium, Glucose, Calcium, Phosphate Levels in Blood at Indicated Time Points | Phosphate; Day 1; n= 18, 20, 20, 22, 22 | 1.318 Millimoles per liter (mmol/L) | Standard Deviation 0.3647 |
| Dapro 25 mg | Sodium, Potassium, Glucose, Calcium, Phosphate Levels in Blood at Indicated Time Points | Sodium; Day 29; n= 17, 19, 18, 19, 17 | 138.8 Millimoles per liter (mmol/L) | Standard Deviation 2.74 |
| Dapro 25 mg | Sodium, Potassium, Glucose, Calcium, Phosphate Levels in Blood at Indicated Time Points | Phosphate; Day 15; n= 17, 20, 18, 22, 20 | 1.348 Millimoles per liter (mmol/L) | Standard Deviation 0.3138 |
| Dapro 25 mg | Sodium, Potassium, Glucose, Calcium, Phosphate Levels in Blood at Indicated Time Points | Glucose; Day 15; n= 17, 20, 18, 22, 20 | 7.26 Millimoles per liter (mmol/L) | Standard Deviation 2.852 |
| Dapro 25 mg | Sodium, Potassium, Glucose, Calcium, Phosphate Levels in Blood at Indicated Time Points | Sodium; Day 15; n= 17, 20, 18, 22, 20 | 138.0 Millimoles per liter (mmol/L) | Standard Deviation 2.36 |
| Dapro 25 mg | Sodium, Potassium, Glucose, Calcium, Phosphate Levels in Blood at Indicated Time Points | Glucose; Day 29; n= 17, 19, 18, 19, 17 | 7.77 Millimoles per liter (mmol/L) | Standard Deviation 4.621 |
| Dapro 25 mg | Sodium, Potassium, Glucose, Calcium, Phosphate Levels in Blood at Indicated Time Points | Glucose; Day 1; n= 18, 20, 20, 22, 22 | 7.05 Millimoles per liter (mmol/L) | Standard Deviation 2.491 |
| Dapro 30 mg | Sodium, Potassium, Glucose, Calcium, Phosphate Levels in Blood at Indicated Time Points | Glucose; Day 43; n= 15, 20, 18, 21, 21 | 8.93 Millimoles per liter (mmol/L) | Standard Deviation 4.28 |
| Dapro 30 mg | Sodium, Potassium, Glucose, Calcium, Phosphate Levels in Blood at Indicated Time Points | Sodium; Day 29; n= 17, 19, 18, 19, 17 | 137.1 Millimoles per liter (mmol/L) | Standard Deviation 2.46 |
| Dapro 30 mg | Sodium, Potassium, Glucose, Calcium, Phosphate Levels in Blood at Indicated Time Points | Potassium; Day 29; n= 17, 19, 18, 19, 17 | 4.96 Millimoles per liter (mmol/L) | Standard Deviation 0.941 |
| Dapro 30 mg | Sodium, Potassium, Glucose, Calcium, Phosphate Levels in Blood at Indicated Time Points | Glucose; Day 1; n= 18, 20, 20, 22, 22 | 8.95 Millimoles per liter (mmol/L) | Standard Deviation 5.012 |
| Dapro 30 mg | Sodium, Potassium, Glucose, Calcium, Phosphate Levels in Blood at Indicated Time Points | Potassium; Day 43; n= 15, 20, 18, 21, 21 | 4.80 Millimoles per liter (mmol/L) | Standard Deviation 0.946 |
| Dapro 30 mg | Sodium, Potassium, Glucose, Calcium, Phosphate Levels in Blood at Indicated Time Points | Calcium corrected; Day 1; n= 18, 20, 20, 22, 22 | 2.215 Millimoles per liter (mmol/L) | Standard Deviation 0.1163 |
| Dapro 30 mg | Sodium, Potassium, Glucose, Calcium, Phosphate Levels in Blood at Indicated Time Points | Phosphate; Day 1; n= 18, 20, 20, 22, 22 | 1.566 Millimoles per liter (mmol/L) | Standard Deviation 0.4269 |
| Dapro 30 mg | Sodium, Potassium, Glucose, Calcium, Phosphate Levels in Blood at Indicated Time Points | Sodium; Day 1; n= 18, 20, 20, 22, 22 | 138.4 Millimoles per liter (mmol/L) | Standard Deviation 1.76 |
| Dapro 30 mg | Sodium, Potassium, Glucose, Calcium, Phosphate Levels in Blood at Indicated Time Points | Sodium; Day 15; n= 17, 20, 18, 22, 20 | 137.2 Millimoles per liter (mmol/L) | Standard Deviation 1.74 |
| Dapro 30 mg | Sodium, Potassium, Glucose, Calcium, Phosphate Levels in Blood at Indicated Time Points | Calcium corrected; Day 15; n= 17, 20, 18, 22, 20 | 2.203 Millimoles per liter (mmol/L) | Standard Deviation 0.1111 |
| Dapro 30 mg | Sodium, Potassium, Glucose, Calcium, Phosphate Levels in Blood at Indicated Time Points | Potassium; Day 15; n= 17, 20, 18, 22, 20 | 4.80 Millimoles per liter (mmol/L) | Standard Deviation 0.791 |
| Dapro 30 mg | Sodium, Potassium, Glucose, Calcium, Phosphate Levels in Blood at Indicated Time Points | Phosphate; Day 43; n= 15, 20, 18, 21, 21 | 1.398 Millimoles per liter (mmol/L) | Standard Deviation 0.4718 |
| Dapro 30 mg | Sodium, Potassium, Glucose, Calcium, Phosphate Levels in Blood at Indicated Time Points | Phosphate; Day 29; n= 17, 19, 18, 19, 17 | 1.550 Millimoles per liter (mmol/L) | Standard Deviation 0.3575 |
| Dapro 30 mg | Sodium, Potassium, Glucose, Calcium, Phosphate Levels in Blood at Indicated Time Points | Glucose; Day 29; n= 17, 19, 18, 19, 17 | 8.75 Millimoles per liter (mmol/L) | Standard Deviation 5.708 |
| Dapro 30 mg | Sodium, Potassium, Glucose, Calcium, Phosphate Levels in Blood at Indicated Time Points | Calcium corrected; Day 29; n= 17, 19, 18, 19, 17 | 2.225 Millimoles per liter (mmol/L) | Standard Deviation 0.181 |
| Dapro 30 mg | Sodium, Potassium, Glucose, Calcium, Phosphate Levels in Blood at Indicated Time Points | Potassium; Day 1; n= 18, 20, 20, 22, 22 | 4.83 Millimoles per liter (mmol/L) | Standard Deviation 0.685 |
| Dapro 30 mg | Sodium, Potassium, Glucose, Calcium, Phosphate Levels in Blood at Indicated Time Points | Sodium; Day 43; n= 15, 20, 18, 21, 21 | 137.6 Millimoles per liter (mmol/L) | Standard Deviation 1.88 |
| Dapro 30 mg | Sodium, Potassium, Glucose, Calcium, Phosphate Levels in Blood at Indicated Time Points | Phosphate; Day 15; n= 17, 20, 18, 22, 20 | 1.645 Millimoles per liter (mmol/L) | Standard Deviation 0.4785 |
| Dapro 30 mg | Sodium, Potassium, Glucose, Calcium, Phosphate Levels in Blood at Indicated Time Points | Glucose; Day 15; n= 17, 20, 18, 22, 20 | 8.67 Millimoles per liter (mmol/L) | Standard Deviation 4.198 |
| Dapro 30 mg | Sodium, Potassium, Glucose, Calcium, Phosphate Levels in Blood at Indicated Time Points | Calcium corrected; Day 43; n= 15, 20, 18, 21, 21 | 2.256 Millimoles per liter (mmol/L) | Standard Deviation 0.1473 |
Secondary
Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Pre-dialysis and Post-dialysis
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Pre-dialysis and Post-dialysis | DBP; pre-dialysis; Day 1; n= 19, 20, 20, 22, 22 | 71.9 Millimeter of mercury (mmHg) | Standard Deviation 14.84 |
| Placebo | Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Pre-dialysis and Post-dialysis | SBP; pre-dialysis; Day 1; n= 19, 20, 20, 22, 22 | 142.5 Millimeter of mercury (mmHg) | Standard Deviation 22.15 |
| Placebo | Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Pre-dialysis and Post-dialysis | SBP; pre-dialysis; Day 15; n= 17, 20, 18, 22, 21 | 138.8 Millimeter of mercury (mmHg) | Standard Deviation 24.12 |
| Placebo | Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Pre-dialysis and Post-dialysis | SBP; pre-dialysis; Day 29; n= 17, 19, 18, 19, 17 | 143.0 Millimeter of mercury (mmHg) | Standard Deviation 22.08 |
| Placebo | Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Pre-dialysis and Post-dialysis | SBP; pre-dialysis; Day 43; n= 16, 20, 19, 21, 21 | 140.0 Millimeter of mercury (mmHg) | Standard Deviation 22.01 |
| Placebo | Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Pre-dialysis and Post-dialysis | DBP; pre-dialysis; Day 15; n= 17, 20, 18, 22, 21 | 72.5 Millimeter of mercury (mmHg) | Standard Deviation 17.76 |
| Placebo | Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Pre-dialysis and Post-dialysis | DBP; pre-dialysis; Day 29; n= 17, 19, 18, 19, 17 | 70.4 Millimeter of mercury (mmHg) | Standard Deviation 15.43 |
| Placebo | Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Pre-dialysis and Post-dialysis | DBP; pre-dialysis; Day 43; n= 16, 20, 19, 21, 21 | 72.5 Millimeter of mercury (mmHg) | Standard Deviation 14.73 |
| Placebo | Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Pre-dialysis and Post-dialysis | SBP; post-dialysis; Day 1; n= 19, 20, 20, 22, 22 | 138.6 Millimeter of mercury (mmHg) | Standard Deviation 18.57 |
| Placebo | Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Pre-dialysis and Post-dialysis | SBP; post-dialysis; Day 15; n= 17, 20, 18, 22, 21 | 138.6 Millimeter of mercury (mmHg) | Standard Deviation 21.83 |
| Placebo | Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Pre-dialysis and Post-dialysis | SBP; post-dialysis; Day 29; n= 17, 19, 18, 19, 17 | 135.7 Millimeter of mercury (mmHg) | Standard Deviation 26.04 |
| Placebo | Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Pre-dialysis and Post-dialysis | SBP; post-dialysis; Day 43; n= 16, 20, 19, 21, 21 | 137.5 Millimeter of mercury (mmHg) | Standard Deviation 22.74 |
| Placebo | Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Pre-dialysis and Post-dialysis | DBP; post-dialysis; Day 1; n= 19, 20, 20, 22, 22 | 72.1 Millimeter of mercury (mmHg) | Standard Deviation 15.11 |
| Placebo | Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Pre-dialysis and Post-dialysis | DBP; post-dialysis; Day 15; n= 17, 20, 18, 22, 21 | 72.4 Millimeter of mercury (mmHg) | Standard Deviation 16.41 |
| Placebo | Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Pre-dialysis and Post-dialysis | DBP; post-dialysis; Day 29; n= 17, 19, 18, 19, 17 | 73.9 Millimeter of mercury (mmHg) | Standard Deviation 15.11 |
| Placebo | Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Pre-dialysis and Post-dialysis | DBP; post-dialysis; Day 43; n= 16, 20, 19, 21, 21 | 69.5 Millimeter of mercury (mmHg) | Standard Deviation 15.24 |
| Dapro 10 mg | Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Pre-dialysis and Post-dialysis | SBP; pre-dialysis; Day 43; n= 16, 20, 19, 21, 21 | 137.9 Millimeter of mercury (mmHg) | Standard Deviation 13.21 |
| Dapro 10 mg | Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Pre-dialysis and Post-dialysis | SBP; post-dialysis; Day 15; n= 17, 20, 18, 22, 21 | 135.5 Millimeter of mercury (mmHg) | Standard Deviation 21.63 |
| Dapro 10 mg | Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Pre-dialysis and Post-dialysis | SBP; post-dialysis; Day 1; n= 19, 20, 20, 22, 22 | 137.0 Millimeter of mercury (mmHg) | Standard Deviation 22.1 |
| Dapro 10 mg | Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Pre-dialysis and Post-dialysis | DBP; post-dialysis; Day 29; n= 17, 19, 18, 19, 17 | 64.4 Millimeter of mercury (mmHg) | Standard Deviation 9.83 |
| Dapro 10 mg | Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Pre-dialysis and Post-dialysis | DBP; pre-dialysis; Day 43; n= 16, 20, 19, 21, 21 | 66.8 Millimeter of mercury (mmHg) | Standard Deviation 11.94 |
| Dapro 10 mg | Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Pre-dialysis and Post-dialysis | DBP; pre-dialysis; Day 1; n= 19, 20, 20, 22, 22 | 68.8 Millimeter of mercury (mmHg) | Standard Deviation 11.02 |
| Dapro 10 mg | Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Pre-dialysis and Post-dialysis | SBP; pre-dialysis; Day 15; n= 17, 20, 18, 22, 21 | 138.3 Millimeter of mercury (mmHg) | Standard Deviation 16.14 |
| Dapro 10 mg | Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Pre-dialysis and Post-dialysis | DBP; post-dialysis; Day 15; n= 17, 20, 18, 22, 21 | 70.1 Millimeter of mercury (mmHg) | Standard Deviation 12.84 |
| Dapro 10 mg | Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Pre-dialysis and Post-dialysis | SBP; pre-dialysis; Day 1; n= 19, 20, 20, 22, 22 | 136.6 Millimeter of mercury (mmHg) | Standard Deviation 15.39 |
| Dapro 10 mg | Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Pre-dialysis and Post-dialysis | DBP; post-dialysis; Day 1; n= 19, 20, 20, 22, 22 | 67.9 Millimeter of mercury (mmHg) | Standard Deviation 11.49 |
| Dapro 10 mg | Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Pre-dialysis and Post-dialysis | DBP; pre-dialysis; Day 15; n= 17, 20, 18, 22, 21 | 70.0 Millimeter of mercury (mmHg) | Standard Deviation 11.92 |
| Dapro 10 mg | Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Pre-dialysis and Post-dialysis | SBP; pre-dialysis; Day 29; n= 17, 19, 18, 19, 17 | 133.1 Millimeter of mercury (mmHg) | Standard Deviation 18.65 |
| Dapro 10 mg | Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Pre-dialysis and Post-dialysis | DBP; post-dialysis; Day 43; n= 16, 20, 19, 21, 21 | 67.4 Millimeter of mercury (mmHg) | Standard Deviation 10.9 |
| Dapro 10 mg | Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Pre-dialysis and Post-dialysis | SBP; post-dialysis; Day 43; n= 16, 20, 19, 21, 21 | 135.8 Millimeter of mercury (mmHg) | Standard Deviation 21.05 |
| Dapro 10 mg | Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Pre-dialysis and Post-dialysis | SBP; post-dialysis; Day 29; n= 17, 19, 18, 19, 17 | 130.1 Millimeter of mercury (mmHg) | Standard Deviation 18.5 |
| Dapro 10 mg | Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Pre-dialysis and Post-dialysis | DBP; pre-dialysis; Day 29; n= 17, 19, 18, 19, 17 | 63.5 Millimeter of mercury (mmHg) | Standard Deviation 13.55 |
| Dapro 15 mg | Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Pre-dialysis and Post-dialysis | DBP; pre-dialysis; Day 29; n= 17, 19, 18, 19, 17 | 70.9 Millimeter of mercury (mmHg) | Standard Deviation 12.86 |
| Dapro 15 mg | Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Pre-dialysis and Post-dialysis | SBP; pre-dialysis; Day 43; n= 16, 20, 19, 21, 21 | 142.0 Millimeter of mercury (mmHg) | Standard Deviation 24.23 |
| Dapro 15 mg | Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Pre-dialysis and Post-dialysis | SBP; pre-dialysis; Day 15; n= 17, 20, 18, 22, 21 | 139.0 Millimeter of mercury (mmHg) | Standard Deviation 22.77 |
| Dapro 15 mg | Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Pre-dialysis and Post-dialysis | DBP; pre-dialysis; Day 1; n= 19, 20, 20, 22, 22 | 73.3 Millimeter of mercury (mmHg) | Standard Deviation 12.96 |
| Dapro 15 mg | Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Pre-dialysis and Post-dialysis | DBP; pre-dialysis; Day 15; n= 17, 20, 18, 22, 21 | 70.1 Millimeter of mercury (mmHg) | Standard Deviation 10.5 |
| Dapro 15 mg | Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Pre-dialysis and Post-dialysis | DBP; pre-dialysis; Day 43; n= 16, 20, 19, 21, 21 | 69.9 Millimeter of mercury (mmHg) | Standard Deviation 13.54 |
| Dapro 15 mg | Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Pre-dialysis and Post-dialysis | DBP; post-dialysis; Day 29; n= 17, 19, 18, 19, 17 | 67.9 Millimeter of mercury (mmHg) | Standard Deviation 12 |
| Dapro 15 mg | Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Pre-dialysis and Post-dialysis | SBP; post-dialysis; Day 1; n= 19, 20, 20, 22, 22 | 139.9 Millimeter of mercury (mmHg) | Standard Deviation 22.24 |
| Dapro 15 mg | Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Pre-dialysis and Post-dialysis | SBP; post-dialysis; Day 15; n= 17, 20, 18, 22, 21 | 137.7 Millimeter of mercury (mmHg) | Standard Deviation 23.02 |
| Dapro 15 mg | Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Pre-dialysis and Post-dialysis | SBP; post-dialysis; Day 29; n= 17, 19, 18, 19, 17 | 133.7 Millimeter of mercury (mmHg) | Standard Deviation 23.88 |
| Dapro 15 mg | Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Pre-dialysis and Post-dialysis | SBP; post-dialysis; Day 43; n= 16, 20, 19, 21, 21 | 130.4 Millimeter of mercury (mmHg) | Standard Deviation 15.47 |
| Dapro 15 mg | Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Pre-dialysis and Post-dialysis | DBP; post-dialysis; Day 1; n= 19, 20, 20, 22, 22 | 68.7 Millimeter of mercury (mmHg) | Standard Deviation 11.64 |
| Dapro 15 mg | Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Pre-dialysis and Post-dialysis | DBP; post-dialysis; Day 43; n= 16, 20, 19, 21, 21 | 67.4 Millimeter of mercury (mmHg) | Standard Deviation 11.24 |
| Dapro 15 mg | Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Pre-dialysis and Post-dialysis | SBP; pre-dialysis; Day 1; n= 19, 20, 20, 22, 22 | 149.2 Millimeter of mercury (mmHg) | Standard Deviation 26.36 |
| Dapro 15 mg | Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Pre-dialysis and Post-dialysis | DBP; post-dialysis; Day 15; n= 17, 20, 18, 22, 21 | 67.8 Millimeter of mercury (mmHg) | Standard Deviation 11.1 |
| Dapro 15 mg | Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Pre-dialysis and Post-dialysis | SBP; pre-dialysis; Day 29; n= 17, 19, 18, 19, 17 | 143.1 Millimeter of mercury (mmHg) | Standard Deviation 23.21 |
| Dapro 25 mg | Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Pre-dialysis and Post-dialysis | SBP; post-dialysis; Day 15; n= 17, 20, 18, 22, 21 | 137.4 Millimeter of mercury (mmHg) | Standard Deviation 17.58 |
| Dapro 25 mg | Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Pre-dialysis and Post-dialysis | DBP; post-dialysis; Day 43; n= 16, 20, 19, 21, 21 | 72.9 Millimeter of mercury (mmHg) | Standard Deviation 12.6 |
| Dapro 25 mg | Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Pre-dialysis and Post-dialysis | SBP; post-dialysis; Day 29; n= 17, 19, 18, 19, 17 | 142.8 Millimeter of mercury (mmHg) | Standard Deviation 23.96 |
| Dapro 25 mg | Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Pre-dialysis and Post-dialysis | SBP; post-dialysis; Day 43; n= 16, 20, 19, 21, 21 | 145.2 Millimeter of mercury (mmHg) | Standard Deviation 20.66 |
| Dapro 25 mg | Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Pre-dialysis and Post-dialysis | DBP; pre-dialysis; Day 15; n= 17, 20, 18, 22, 21 | 73.5 Millimeter of mercury (mmHg) | Standard Deviation 13.69 |
| Dapro 25 mg | Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Pre-dialysis and Post-dialysis | SBP; pre-dialysis; Day 43; n= 16, 20, 19, 21, 21 | 149.0 Millimeter of mercury (mmHg) | Standard Deviation 23.32 |
| Dapro 25 mg | Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Pre-dialysis and Post-dialysis | DBP; post-dialysis; Day 1; n= 19, 20, 20, 22, 22 | 71.1 Millimeter of mercury (mmHg) | Standard Deviation 12.92 |
| Dapro 25 mg | Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Pre-dialysis and Post-dialysis | DBP; post-dialysis; Day 15; n= 17, 20, 18, 22, 21 | 71.3 Millimeter of mercury (mmHg) | Standard Deviation 11.07 |
| Dapro 25 mg | Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Pre-dialysis and Post-dialysis | SBP; pre-dialysis; Day 29; n= 17, 19, 18, 19, 17 | 144.2 Millimeter of mercury (mmHg) | Standard Deviation 23.27 |
| Dapro 25 mg | Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Pre-dialysis and Post-dialysis | SBP; pre-dialysis; Day 1; n= 19, 20, 20, 22, 22 | 144.1 Millimeter of mercury (mmHg) | Standard Deviation 24.27 |
| Dapro 25 mg | Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Pre-dialysis and Post-dialysis | DBP; pre-dialysis; Day 43; n= 16, 20, 19, 21, 21 | 77.9 Millimeter of mercury (mmHg) | Standard Deviation 16.03 |
| Dapro 25 mg | Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Pre-dialysis and Post-dialysis | DBP; pre-dialysis; Day 1; n= 19, 20, 20, 22, 22 | 71.8 Millimeter of mercury (mmHg) | Standard Deviation 14.38 |
| Dapro 25 mg | Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Pre-dialysis and Post-dialysis | SBP; post-dialysis; Day 1; n= 19, 20, 20, 22, 22 | 136.7 Millimeter of mercury (mmHg) | Standard Deviation 21.15 |
| Dapro 25 mg | Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Pre-dialysis and Post-dialysis | DBP; post-dialysis; Day 29; n= 17, 19, 18, 19, 17 | 72.4 Millimeter of mercury (mmHg) | Standard Deviation 12.43 |
| Dapro 25 mg | Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Pre-dialysis and Post-dialysis | DBP; pre-dialysis; Day 29; n= 17, 19, 18, 19, 17 | 73.3 Millimeter of mercury (mmHg) | Standard Deviation 13.17 |
| Dapro 25 mg | Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Pre-dialysis and Post-dialysis | SBP; pre-dialysis; Day 15; n= 17, 20, 18, 22, 21 | 146.6 Millimeter of mercury (mmHg) | Standard Deviation 20.75 |
| Dapro 30 mg | Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Pre-dialysis and Post-dialysis | DBP; post-dialysis; Day 1; n= 19, 20, 20, 22, 22 | 71.5 Millimeter of mercury (mmHg) | Standard Deviation 11.17 |
| Dapro 30 mg | Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Pre-dialysis and Post-dialysis | SBP; post-dialysis; Day 15; n= 17, 20, 18, 22, 21 | 140.9 Millimeter of mercury (mmHg) | Standard Deviation 15.34 |
| Dapro 30 mg | Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Pre-dialysis and Post-dialysis | DBP; post-dialysis; Day 29; n= 17, 19, 18, 19, 17 | 72.9 Millimeter of mercury (mmHg) | Standard Deviation 11.18 |
| Dapro 30 mg | Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Pre-dialysis and Post-dialysis | DBP; pre-dialysis; Day 43; n= 16, 20, 19, 21, 21 | 72.8 Millimeter of mercury (mmHg) | Standard Deviation 10.52 |
| Dapro 30 mg | Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Pre-dialysis and Post-dialysis | SBP; pre-dialysis; Day 15; n= 17, 20, 18, 22, 21 | 142.3 Millimeter of mercury (mmHg) | Standard Deviation 14.9 |
| Dapro 30 mg | Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Pre-dialysis and Post-dialysis | DBP; pre-dialysis; Day 1; n= 19, 20, 20, 22, 22 | 72.2 Millimeter of mercury (mmHg) | Standard Deviation 13.64 |
| Dapro 30 mg | Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Pre-dialysis and Post-dialysis | SBP; post-dialysis; Day 29; n= 17, 19, 18, 19, 17 | 147.8 Millimeter of mercury (mmHg) | Standard Deviation 19.09 |
| Dapro 30 mg | Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Pre-dialysis and Post-dialysis | DBP; post-dialysis; Day 43; n= 16, 20, 19, 21, 21 | 75.3 Millimeter of mercury (mmHg) | Standard Deviation 7.89 |
| Dapro 30 mg | Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Pre-dialysis and Post-dialysis | DBP; pre-dialysis; Day 15; n= 17, 20, 18, 22, 21 | 69.7 Millimeter of mercury (mmHg) | Standard Deviation 12.43 |
| Dapro 30 mg | Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Pre-dialysis and Post-dialysis | SBP; pre-dialysis; Day 29; n= 17, 19, 18, 19, 17 | 148.7 Millimeter of mercury (mmHg) | Standard Deviation 19.17 |
| Dapro 30 mg | Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Pre-dialysis and Post-dialysis | SBP; post-dialysis; Day 1; n= 19, 20, 20, 22, 22 | 140.1 Millimeter of mercury (mmHg) | Standard Deviation 20.1 |
| Dapro 30 mg | Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Pre-dialysis and Post-dialysis | SBP; post-dialysis; Day 43; n= 16, 20, 19, 21, 21 | 137.5 Millimeter of mercury (mmHg) | Standard Deviation 22.74 |
| Dapro 30 mg | Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Pre-dialysis and Post-dialysis | DBP; pre-dialysis; Day 29; n= 17, 19, 18, 19, 17 | 72.7 Millimeter of mercury (mmHg) | Standard Deviation 9.96 |
| Dapro 30 mg | Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Pre-dialysis and Post-dialysis | DBP; post-dialysis; Day 15; n= 17, 20, 18, 22, 21 | 71.1 Millimeter of mercury (mmHg) | Standard Deviation 9.51 |
| Dapro 30 mg | Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Pre-dialysis and Post-dialysis | SBP; pre-dialysis; Day 1; n= 19, 20, 20, 22, 22 | 144.1 Millimeter of mercury (mmHg) | Standard Deviation 17.01 |
| Dapro 30 mg | Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Pre-dialysis and Post-dialysis | SBP; pre-dialysis; Day 43; n= 16, 20, 19, 21, 21 | 147.1 Millimeter of mercury (mmHg) | Standard Deviation 19.18 |
Secondary
Time to Reach Cmax (Tmax) and Apparent Terminal Half-life (t1/2) of Dapro
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
Population: 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 | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Time to Reach Cmax (Tmax) and Apparent Terminal Half-life (t1/2) of Dapro | Tmax; n= 19, 15, 16, 14 | 2.456 Hour | Geometric Coefficient of Variation 78.9 |
| Placebo | Time to Reach Cmax (Tmax) and Apparent Terminal Half-life (t1/2) of Dapro | T1/2; n= 12, 9, 8, 11 | 2.086 Hour | Geometric Coefficient of Variation 50 |
| Dapro 10 mg | Time to Reach Cmax (Tmax) and Apparent Terminal Half-life (t1/2) of Dapro | T1/2; n= 12, 9, 8, 11 | 1.886 Hour | Geometric Coefficient of Variation 62.3 |
| Dapro 10 mg | Time to Reach Cmax (Tmax) and Apparent Terminal Half-life (t1/2) of Dapro | Tmax; n= 19, 15, 16, 14 | 2.106 Hour | Geometric Coefficient of Variation 82.1 |
| Dapro 15 mg | Time to Reach Cmax (Tmax) and Apparent Terminal Half-life (t1/2) of Dapro | Tmax; n= 19, 15, 16, 14 | 2.297 Hour | Geometric Coefficient of Variation 96.5 |
| Dapro 15 mg | Time to Reach Cmax (Tmax) and Apparent Terminal Half-life (t1/2) of Dapro | T1/2; n= 12, 9, 8, 11 | 1.418 Hour | Geometric Coefficient of Variation 58.4 |
| Dapro 25 mg | Time to Reach Cmax (Tmax) and Apparent Terminal Half-life (t1/2) of Dapro | Tmax; n= 19, 15, 16, 14 | 1.718 Hour | Geometric Coefficient of Variation 58 |
| Dapro 25 mg | Time to Reach Cmax (Tmax) and Apparent Terminal Half-life (t1/2) of Dapro | T1/2; n= 12, 9, 8, 11 | 2.897 Hour | Geometric Coefficient of Variation 38.7 |
Secondary
Weight Values at Post-dialysis
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Weight Values at Post-dialysis | Day 1; n= 19, 20, 20, 22, 22 | 82.38 Kilograms (kg) | Standard Deviation 25.941 |
| Placebo | Weight Values at Post-dialysis | Day 15; n= 17, 20, 18, 22, 21 | 84.24 Kilograms (kg) | Standard Deviation 26.652 |
| Placebo | Weight Values at Post-dialysis | Day 29; n= 17, 19, 18, 19, 17 | 83.22 Kilograms (kg) | Standard Deviation 27.198 |
| Placebo | Weight Values at Post-dialysis | Day 43; n= 16, 20, 19, 21, 21 | 83.93 Kilograms (kg) | Standard Deviation 27.589 |
| Dapro 10 mg | Weight Values at Post-dialysis | Day 1; n= 19, 20, 20, 22, 22 | 80.04 Kilograms (kg) | Standard Deviation 25.996 |
| Dapro 10 mg | Weight Values at Post-dialysis | Day 43; n= 16, 20, 19, 21, 21 | 80.21 Kilograms (kg) | Standard Deviation 26.683 |
| Dapro 10 mg | Weight Values at Post-dialysis | Day 15; n= 17, 20, 18, 22, 21 | 80.00 Kilograms (kg) | Standard Deviation 25.887 |
| Dapro 10 mg | Weight Values at Post-dialysis | Day 29; n= 17, 19, 18, 19, 17 | 81.04 Kilograms (kg) | Standard Deviation 25.925 |
| Dapro 15 mg | Weight Values at Post-dialysis | Day 43; n= 16, 20, 19, 21, 21 | 79.25 Kilograms (kg) | Standard Deviation 21.757 |
| Dapro 15 mg | Weight Values at Post-dialysis | Day 15; n= 17, 20, 18, 22, 21 | 79.82 Kilograms (kg) | Standard Deviation 22.2 |
| Dapro 15 mg | Weight Values at Post-dialysis | Day 29; n= 17, 19, 18, 19, 17 | 80.02 Kilograms (kg) | Standard Deviation 22.286 |
| Dapro 15 mg | Weight Values at Post-dialysis | Day 1; n= 19, 20, 20, 22, 22 | 78.83 Kilograms (kg) | Standard Deviation 21.331 |
| Dapro 25 mg | Weight Values at Post-dialysis | Day 1; n= 19, 20, 20, 22, 22 | 79.38 Kilograms (kg) | Standard Deviation 23.345 |
| Dapro 25 mg | Weight Values at Post-dialysis | Day 15; n= 17, 20, 18, 22, 21 | 79.44 Kilograms (kg) | Standard Deviation 23.5 |
| Dapro 25 mg | Weight Values at Post-dialysis | Day 43; n= 16, 20, 19, 21, 21 | 80.64 Kilograms (kg) | Standard Deviation 23.347 |
| Dapro 25 mg | Weight Values at Post-dialysis | Day 29; n= 17, 19, 18, 19, 17 | 82.66 Kilograms (kg) | Standard Deviation 23.036 |
| Dapro 30 mg | Weight Values at Post-dialysis | Day 43; n= 16, 20, 19, 21, 21 | 73.66 Kilograms (kg) | Standard Deviation 11.614 |
| Dapro 30 mg | Weight Values at Post-dialysis | Day 29; n= 17, 19, 18, 19, 17 | 76.07 Kilograms (kg) | Standard Deviation 18.135 |
| Dapro 30 mg | Weight Values at Post-dialysis | Day 15; n= 17, 20, 18, 22, 21 | 75.55 Kilograms (kg) | Standard Deviation 17.595 |
| Dapro 30 mg | Weight Values at Post-dialysis | Day 1; n= 19, 20, 20, 22, 22 | 76.03 Kilograms (kg) | Standard Deviation 16.877 |