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    Clinical Trial Results:
    A 29-day, randomized, double-blinded, placebo-controlled, parallel-group, multi-center study to evaluate the efficacy, safety and pharmacokinetics of three-times weekly dosing of GSK1278863 in hemodialysis-dependent subjects with anemia associated with chronic kidney disease who are switched from a stable dose of an erythropoiesis-stimulating agent.

    Summary
    EudraCT number
    		 2015-004790-32
    Trial protocol
    		 ES   DE  
    Global end of trial date
    25 Jan 2017

    Results information
    Results version number
    		 v3(current)
    This version publication date
    02 May 2018
    First version publication date
    27 Jan 2018
    Other versions
    		 v1 , v2
    Version creation reason

    Trial information

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    Trial identification
    Sponsor protocol code
    204836
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    GlaxoSmithKline
    Sponsor organisation address
    980 Great West Road, Brentford, Middlesex, United Kingdom,
    Public contact
    GSK Response Center, GlaxoSmithKline, 1 866-435-7343,
    Scientific contact
    GSK Response Center, GlaxoSmithKline, 1 866-435-7343,
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    01 May 2017
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    25 Jan 2017
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    Characterize the dose-response relationship between GSK1278863 administered three-times weekly and hemoglobin (Hgb) at Day 29.
    Protection of trial subjects
    The protocol included stopping criteria for hemoglobin (including limits for both increases and decreases) for the participants’ safety
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    17 Feb 2016
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    United States: 47
    Country: Number of subjects enrolled
    Spain: 28
    Country: Number of subjects enrolled
    Canada: 10
    Country: Number of subjects enrolled
    Russian Federation: 14
    Country: Number of subjects enrolled
    Germany: 4
    Worldwide total number of subjects
    103
    EEA total number of subjects
    32
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    53
    From 65 to 84 years
    45
    85 years and over
    5

    Subject disposition

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    Recruitment
    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
    Screening 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.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Investigator, Subject

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Placebo
    Arm description
    		 Randomized participants received placebo tablet via oral route three times weekly for 29 days.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Placebo tablets will be available as round, biconvex, white film coated tablets. Placebo tablets were administered three times weekly for 29 days via oral route.

    Arm title
    		 Dapro 10 mg
    Arm description
    		 Randomized participants received dapro 10 mg tablet via oral route three times weekly for 29 days.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Daprodustat
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Daprodustat tablets will be available as round, biconvex, white film coated tablets. Daprodustat tablets were administered three times weekly for 29 days via oral route.

    Arm title
    		 Dapro 15 mg
    Arm description
    		 Randomized participants received dapro 15 mg tablet via oral route three times weekly for 29 days.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Daprodustat
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Daprodustat tablets will be available as round, biconvex, white film coated tablets. Daprodustat tablets were administered three times weekly for 29 days via oral route.

    Arm title
    		 Dapro 25 mg
    Arm description
    		 Randomized participants received dapro 25 mg tablet via oral route three times weekly for 29 days.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Daprodustat
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Daprodustat tablets will be available as round, biconvex, white film coated tablets. Daprodustat tablets were administered three times weekly for 29 days via oral route.

    Arm title
    		 Dapro 30 mg
    Arm description
    		 Randomized participants received dapro 30 mg tablet via oral route three times weekly for 29 days
    Arm type
    		 Experimental

    Investigational medicinal product name
    Daprodustat
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Daprodustat tablets will be available as round, biconvex, white film coated tablets. Daprodustat tablets were administered three times weekly for 29 days via oral route.

    Number of subjects in period 1
    		Placebo Dapro 10 mg Dapro 15 mg Dapro 25 mg Dapro 30 mg
    Started
    20
    20
    20
    21
    22
    Completed
    17
    19
    16
    17
    14
    Not completed
    3
    1
    4
    4
    8
         Physician decision
    1
    -
    -
    -
    -
         Consent withdrawn by subject
    1
    -
    1
    -
    -
         Other: Reached stopping criteria
    -
    1
    2
    3
    4
         Adverse event, non-fatal
    -
    -
    1
    -
    2
         Protocol deviation
    1
    -
    -
    1
    2

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Randomized participants received placebo tablet via oral route three times weekly for 29 days.

    Reporting group title
    Dapro 10 mg
    Reporting group description
    		 Randomized participants received dapro 10 mg tablet via oral route three times weekly for 29 days.

    Reporting group title
    Dapro 15 mg
    Reporting group description
    		 Randomized participants received dapro 15 mg tablet via oral route three times weekly for 29 days.

    Reporting group title
    Dapro 25 mg
    Reporting group description
    		 Randomized participants received dapro 25 mg tablet via oral route three times weekly for 29 days.

    Reporting group title
    Dapro 30 mg
    Reporting group description
    		 Randomized participants received dapro 30 mg tablet via oral route three times weekly for 29 days

    Reporting group values
    		 Placebo Dapro 10 mg Dapro 15 mg Dapro 25 mg Dapro 30 mg Total
    Number of subjects
    		 20 20 20 21 22
    Age categorical
    Units: Subjects
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 61.0 ( 13.06 ) 63.6 ( 16.98 ) 59.5 ( 12.26 ) 67.2 ( 15.22 ) 65.4 ( 13.97 ) -
    Gender categorical
    Units: Subjects
        Female
    		 11 8 6 9 8 42
        Male
    		 9 12 14 12 14 61
    Race/Ethnicity, Customized
    Units: Subjects
        African American/African Heritage
    		 6 6 7 5 6 30
        American Indian Or Alaskan Native
    		 0 1 0 0 1 2
        Asian - Central/South Asian Heritage
    		 0 1 1 0 0 2
        Native Hawaiian Or Other Pacific Islander
    		 0 0 0 1 0 1
        White- Arabic/North African Heritage
    		 0 0 0 1 0 1
        White-White/Caucasian/European Heritage
    		 14 12 12 14 15 67

    End points

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    End points reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Randomized participants received placebo tablet via oral route three times weekly for 29 days.

    Reporting group title
    Dapro 10 mg
    Reporting group description
    		 Randomized participants received dapro 10 mg tablet via oral route three times weekly for 29 days.

    Reporting group title
    Dapro 15 mg
    Reporting group description
    		 Randomized participants received dapro 15 mg tablet via oral route three times weekly for 29 days.

    Reporting group title
    Dapro 25 mg
    Reporting group description
    		 Randomized participants received dapro 25 mg tablet via oral route three times weekly for 29 days.

    Reporting group title
    Dapro 30 mg
    Reporting group description
    		 Randomized participants received dapro 30 mg tablet via oral route three times weekly for 29 days

    Subject analysis set title
    Dapro 25 mg
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Randomized participants received dapro 25 mg tablet via oral route three times weekly for 29 days.

    Primary: Change from Baseline in Hgb levels at Day 29

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    End point title
    		 Change from Baseline in Hgb levels at Day 29
    End point description
    Blood samples were collected from participants for measurement of Hgb values. Baseline is the average of Hgb measured at Week -2 and Day 1 visits. Change from Baseline at Day 29 was defined as post dose value at Day 29 minus Baseline value. The analysis was performed on intent-to-treat (ITT) Population which comprised of all randomized participants who received at least one dose of study treatment, had a Baseline and at least one corresponding on treatment assessment, including Hgb.
    End point type
    Primary
    End point timeframe
    Baseline and Day 29
    End point values
    		 Placebo Dapro 10 mg Dapro 15 mg Dapro 25 mg Dapro 30 mg
    Number of subjects analysed
    17 [1]
    19 [2]
    16 [3]
    17 [4]
    15 [5]
    Units: g/dL
    arithmetic mean (standard deviation)
        Category title 1
    -0.61 ( 0.646 )
    -0.19 ( 1.750 )
    -0.13 ( 1.088 )
    0.64 ( 1.453 )
    0.55 ( 1.167 )
    Notes
    [1] - ITT Population
    [2] - ITT Population
    [3] - ITT Population
    [4] - ITT Population
    [5] - ITT Population
    Statistical analysis title
    		 Statistical analysis 1
    Statistical analysis description
    Analysis using a Repeated Measures Model with terms included for baseline, treatment, time and treatment*time. Model-adjusted treatment difference of dapro 10 mg arm from Placebo along with 95 percent CI are presented.
    Comparison groups
    Dapro 10 mg v Placebo
    Number of subjects included in analysis
    36
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0.57
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.31
         upper limit
    		 1.45
    Statistical analysis title
    		 Statistical analysis 2
    Statistical analysis description
    Analysis using a Repeated Measures Model with terms included for baseline, treatment, time and treatment*time. Model-adjusted treatment difference of dapro 15 mg arm from Placebo along with 95 percent CI are presented.
    Comparison groups
    Dapro 15 mg v Placebo
    Number of subjects included in analysis
    33
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0.51
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.4
         upper limit
    		 1.42
    Statistical analysis title
    		 Statistical analysis 3
    Statistical analysis description
    Analysis using a Repeated Measures Model with terms included for baseline, treatment, time and treatment*time. Model-adjusted treatment difference of dapro 25 mg arm from Placebo along with 95 percent CI are presented.
    Comparison groups
    Placebo v Dapro 25 mg
    Number of subjects included in analysis
    34
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Mean difference (final values)
    Point estimate
    1.47
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.59
         upper limit
    		 2.35
    Statistical analysis title
    		 Statistical analysis 4
    Statistical analysis description
    Analysis using a Repeated Measures Model with terms included for baseline, treatment, time and treatment*time. Model-adjusted treatment difference of dapro 30 mg arm from Placebo along with 95 percent CI are presented.
    Comparison groups
    Placebo v Dapro 30 mg
    Number of subjects included in analysis
    32
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Mean difference (final values)
    Point estimate
    1.67
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.77
         upper limit
    		 2.57

    Secondary: Maximum observed change from Baseline in plasma erythropoietin (EPO)

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    End point title
    		 Maximum observed change from Baseline in plasma erythropoietin (EPO)
    End point description
    Blood samples were collected at Day 1, Day 15 and Day 29 for pharmacodynamic analysis of effect of dapro three times weekly dose regimens on EPO. Day 1 values were considered as Baseline values. Change from Baseline was calculated by subtracting post-Baseline visit values minus Baseline value. The change from Baseline at each given post-Baseline time point was calculated and the maximum change from Baseline was determined.
    End point type
    Secondary
    End point timeframe
    Baseline and up to Day 29
    End point values
    		 Placebo Dapro 10 mg Dapro 15 mg Dapro 25 mg Dapro 30 mg
    Number of subjects analysed
    18 [6]
    20 [7]
    18 [8]
    21 [9]
    20 [10]
    Units: International unit per liter (IU/L)
    arithmetic mean (standard deviation)
        Category title 1
    53.761 ( 132.6875 )
    2.255 ( 84.8921 )
    73.369 ( 95.9772 )
    302.529 ( 469.8312 )
    477.644 ( 388.9757 )
    Notes
    [6] - ITT Population
    [7] - ITT Population
    [8] - ITT Population
    [9] - ITT Population
    [10] - ITT Population
    No statistical analyses for this end point

    Secondary: Maximum observed percent change from Baseline in Vascular Endothelial Growth Factor (VEGF)

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    End point title
    		 Maximum observed percent change from Baseline in Vascular Endothelial Growth Factor (VEGF)
    End point description
    Blood samples were collected at Day 1, Day 15 and Day 29 for pharmacodynamic analysis of effect of dapro three times weekly dose regimens on VEGF. Day 1 values were considered as Baseline values. The percent change from Baseline at each given post-Baseline time point was calculated (expressed as geometric mean) and the maximum percent change from Baseline was determined.
    End point type
    Secondary
    End point timeframe
    Baseline and up to Day 29
    End point values
    		 Placebo Dapro 10 mg Dapro 15 mg Dapro 25 mg Dapro 30 mg
    Number of subjects analysed
    18 [11]
    20 [12]
    18 [13]
    21 [14]
    20 [15]
    Units: Nanograms per liter (ng/L)
    geometric mean (confidence interval 95%)
        Category title 1
    20.35 (-0.48 to 45.55)
    43.75 (16.44 to 77.45)
    32.16 (-4.77 to 83.41)
    53.34 (17.17 to 100.68)
    76.09 (34.89 to 129.88)
    Notes
    [11] - ITT Population
    [12] - ITT Population
    [13] - ITT Population
    [14] - ITT Population
    [15] - ITT Population
    No statistical analyses for this end point

    Secondary: Percent change from Baseline in hepcidin at Day 29

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    End point title
    		 Percent change from Baseline in hepcidin at Day 29
    End point description
    Blood samples were collected at Day 1, Day 15 and Day 29 for pharmacodynamic analysis of effect of dapro three times weekly dose regimens on hepcidin. Day 1 values were considered as Baseline values. The Percent change from Baseline at Day 29 post-Baseline time point was calculated and expressed as geometric mean and the maximum change from Baseline was determined.
    End point type
    Secondary
    End point timeframe
    Baseline and Day 29
    End point values
    		 Placebo Dapro 10 mg Dapro 15 mg Dapro 25 mg Dapro 30 mg
    Number of subjects analysed
    17 [16]
    19 [17]
    15 [18]
    17 [19]
    15 [20]
    Units: Micrograms per liter (µg/L)
    geometric mean (confidence interval 95%)
        Category title 1
    27.81 (-12.68 to 87.08)
    35.37 (-1.13 to 85.34)
    3.83 (-17.85 to 31.24)
    -36.74 (-49.91 to -20.12)
    -36.09 (-57.24 to -4.48)
    Notes
    [16] - ITT Population
    [17] - ITT Population
    [18] - ITT Population
    [19] - ITT Population
    [20] - ITT Population
    No statistical analyses for this end point

    Secondary: Change from Baseline in hematocrit levels

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    End point title
    		 Change from Baseline in hematocrit levels
    End point description
    Blood samples were collected at Day 1, Day 15 and Day 29 for pharmacodynamic analysis of effect Dapro three times weekly dose regimens on hematocrit. Day 1 values were considered as Baseline values. Change from Baseline was calculated by subtracting post-dose visit values minus Baseline value. The change from Baseline at Day 29 post-Baseline time point was calculated.
    End point type
    Secondary
    End point timeframe
    Baseline and Day 29
    End point values
    		 Placebo Dapro 10 mg Dapro 15 mg Dapro 25 mg Dapro 30 mg
    Number of subjects analysed
    16 [21]
    19 [22]
    14 [23]
    16 [24]
    15 [25]
    Units: Proportion of red blood cells in blood
    arithmetic mean (standard deviation)
        Category title 1
    -0.0218 ( 0.02469 )
    -0.0127 ( 0.05396 )
    -0.0149 ( 0.05379 )
    0.0150 ( 0.04511 )
    0.0215 ( 0.03852 )
    Notes
    [21] - ITT Population
    [22] - ITT Population
    [23] - ITT Population
    [24] - ITT Population
    [25] - ITT Population
    No statistical analyses for this end point

    Secondary: Change from Baseline in red blood cell (RBC) count

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    End point title
    		 Change from Baseline in red blood cell (RBC) count
    End point description
    Blood samples were collected at Day 1, Day 15 and Day 29 for pharmacodynamic analysis of effect Dapro three times weekly dose regimens on RBC count. Day 1 values were considered as Baseline values. Change from Baseline was calculated by subtracting post-dose visit values minus Baseline value. The change from Baseline at Day 29 post-Baseline time point was calculated.
    End point type
    Secondary
    End point timeframe
    Baseline and Day 29
    End point values
    		 Placebo Dapro 10 mg Dapro 15 mg Dapro 25 mg Dapro 30 mg
    Number of subjects analysed
    16 [26]
    19 [27]
    14 [28]
    16 [29]
    15 [30]
    Units: 10^12 cells/L
    arithmetic mean (standard deviation)
        Category title 1
    -0.19 ( 0.263 )
    -0.12 ( 0.494 )
    -0.13 ( 0.500 )
    0.12 ( 0.420 )
    0.15 ( 0.342 )
    Notes
    [26] - ITT Population
    [27] - ITT Population
    [28] - ITT Population
    [29] - ITT Population
    [30] - ITT Population
    No statistical analyses for this end point

    Secondary: Change from Baseline in reticulocyte count

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    End point title
    		 Change from Baseline in reticulocyte count
    End point description
    Blood samples were collected at Day 1, Day 15 and Day 29 for pharmacodynamic analysis of effect Dapro three times weekly dose regimens on reticulocyte count. Day 1 values were considered as Baseline values. Change from Baseline was calculated by subtracting post-Baseline visit values minus Baseline value. The change from Baseline at Day 29 post-Baseline time point was calculated.
    End point type
    Secondary
    End point timeframe
    Baseline and Day 29
    End point values
    		 Placebo Dapro 10 mg Dapro 15 mg Dapro 25 mg Dapro 30 mg
    Number of subjects analysed
    16 [31]
    18 [32]
    14 [33]
    16 [34]
    15 [35]
    Units: Percentage of reticulocyte
    arithmetic mean (standard deviation)
        Category title 1
    -0.08 ( 0.848 )
    -0.11 ( 0.803 )
    -0.04 ( 0.581 )
    0.43 ( 0.547 )
    0.09 ( 0.695 )
    Notes
    [31] - ITT Population
    [32] - ITT Population
    [33] - ITT Population
    [34] - ITT Population
    [35] - ITT Population
    No statistical analyses for this end point

    Secondary: Change from Baseline in reticulocyte hemoglobin (CHr)

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    End point title
    		 Change from Baseline in reticulocyte hemoglobin (CHr)
    End point description
    Blood samples were collected at Day 1, Day 15 and Day 29 for pharmacodynamic analysis of effect Dapro three times weekly dose regimens on CHr. Day 1 values were considered as Baseline values. Change from Baseline was calculated by subtracting post-Baseline visit values minus Baseline value. The change from Baseline at Day 29 post-Baseline time point was calculated.
    End point type
    Secondary
    End point timeframe
    Baseline and Day 29
    End point values
    		 Placebo Dapro 10 mg Dapro 15 mg Dapro 25 mg Dapro 30 mg
    Number of subjects analysed
    16 [36]
    19 [37]
    14 [38]
    16 [39]
    15 [40]
    Units: Picograms (pg)
    arithmetic mean (standard deviation)
        Category title 1
    -0.15 ( 1.375 )
    0.23 ( 1.335 )
    0.26 ( 1.103 )
    0.23 ( 1.040 )
    0.59 ( 1.436 )
    Notes
    [36] - ITT Population
    [37] - ITT Population
    [38] - ITT Population
    [39] - ITT Population
    [40] - ITT Population
    No statistical analyses for this end point

    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

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    End point title
    		 Area under the curve (AUC) from time zero to the time of the last quantifiable concentration (AUC[0-t]) and AUC from time zero to infinity (AUC[0-inf]) of Dapro [41]
    End point description
    Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of dapro. The data from each PK sampling day was combined to generate a single profile, and normalized to a 24-hour period to create a “Day 1” profile for non-compartmental analysis (NCA). Metabolite plasma concentrations were analyzed but PK parameters could not be calculated as the metabolites were partially eliminated through dialysis and the dialysis start and end times were not consistent on both PK days. Therefore, a representative metabolite PK profile could not be generated. The analysis was performed on PK Population, which comprised of all participants from whom a PK sample has been obtained and analyzed. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). One participant was randomized to the placebo but erroneously received daprodustat 25mg and was included in the 25mg subset analysis group for all PK analyses.
    End point type
    Secondary
    End point timeframe
    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
    Notes
    [41] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period.
    End point values
    		 Dapro 10 mg Dapro 15 mg Dapro 30 mg Dapro 25 mg
    Number of subjects analysed
    20 [42]
    20 [43]
    22 [44]
    22 [45]
    Units: hour into nanograms/milliliter (h*ng/mL)
    geometric mean (geometric coefficient of variation)
        AUC (0-t); n= 19, 15, 14,16
    311.7 ( 91.4 )
    416.7 ( 168.6 )
    1010 ( 92.3 )
    513.9 ( 396.1 )
        AUC (0-inf); n= 12, 9, 11, 8
    348.2 ( 78.2 )
    383.5 ( 142.7 )
    1369 ( 59.3 )
    1214 ( 41.6 )
    Notes
    [42] - PK Population
    [43] - PK Population
    [44] - PK Population
    [45] - PK Population
    No statistical analyses for this end point

    Secondary: Maximum observed concentration of dapro in plasma (Cmax)

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    End point title
    		 Maximum observed concentration of dapro in plasma (Cmax) [46]
    End point description
    Blood samples were collected at indicated time points for PK analysis of dapro. The data from each PK sampling day was combined to generate a single profile, and normalized to a 24-hour period to create a “Day 1” profile for NCA. Metabolite plasma concentrations were analyzed but PK parameters could not be calculated as the metabolites were partially eliminated through dialysis and the dialysis start and end times were not consistent on both PK days. Therefore, a representative metabolite PK profile could not be generated.
    End point type
    Secondary
    End point timeframe
    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
    Notes
    [46] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period.
    End point values
    		 Dapro 10 mg Dapro 15 mg Dapro 25 mg Dapro 30 mg
    Number of subjects analysed
    19 [47]
    15 [48]
    16 [49]
    14 [50]
    Units: ng/mL
    geometric mean (geometric coefficient of variation)
        Category title 1
    140.0 ( 104.0 )
    141.4 ( 248.8 )
    246.9 ( 311.5 )
    387.3 ( 99.4 )
    Notes
    [47] - PK Population
    [48] - PK Population
    [49] - PK Population
    [50] - PK Population
    No statistical analyses for this end point

    Secondary: Time to reach Cmax (Tmax) and Apparent terminal half-life (t1/2) of dapro

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    End point title
    		 Time to reach Cmax (Tmax) and Apparent terminal half-life (t1/2) of dapro [51]
    End point description
    Blood samples were collected at indicated time points for PK analysis of dapro. The data from each PK sampling day was combined to generate a single profile, and normalized to a 24-hour period to create a “Day 1” profile for NCA. Metabolite plasma concentrations were analyzed but PK parameters could not be calculated as the metabolites were partially eliminated through dialysis and the dialysis start and end times were not consistent on both PK days. Therefore, a representative metabolite PK profile could not be generated. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). One participant was randomized to the placebo but erroneously received daprodustat 25mg and was included in the 25mg subset analysis group for all PK analyses.
    End point type
    Secondary
    End point timeframe
    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
    Notes
    [51] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period.
    End point values
    		 Dapro 10 mg Dapro 15 mg Dapro 30 mg Dapro 25 mg
    Number of subjects analysed
    20 [52]
    20 [53]
    22 [54]
    22 [55]
    Units: Hour
    geometric mean (geometric coefficient of variation)
        Tmax; n= 19, 15, 14, 16
    2.456 ( 78.9 )
    2.106 ( 82.1 )
    1.718 ( 58.0 )
    2.297 ( 96.5 )
        T1/2; n= 12, 9, 11, 8
    2.086 ( 50.0 )
    1.886 ( 62.3 )
    2.897 ( 38.7 )
    1.418 ( 58.4 )
    Notes
    [52] - PK Population
    [53] - PK Population
    [54] - PK Population
    [55] - PK Population
    No statistical analyses for this end point

    Secondary: Number of participants who discontinued study treatment

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    End point title
    		 Number of participants who discontinued study treatment [56]
    End point description
    Reasons of study treatment discontinuation included adverse events (AEs), protocol deviation, participants reached protocol defined stopping criteria, physician decision and withdrawal by participants. Number of participants who discontinued study treatment are presented. Analysis was performed on Safety Population which comprised of all participants who received at least one dose of study treatment. One participant was randomized to the placebo but erroneously received daprodustat 25mg and was included in the 25mg subset analysis group for all safety population analyses.
    End point type
    Secondary
    End point timeframe
    Up to Day 43
    Notes
    [56] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period.
    End point values
    		 Placebo Dapro 10 mg Dapro 15 mg Dapro 30 mg Dapro 25 mg
    Number of subjects analysed
    19 [57]
    20 [58]
    20 [59]
    22 [60]
    22 [61]
    Units: Participants
        AEs
    0
    0
    1
    1
    0
        Protocol deviation
    1
    0
    0
    2
    1
        Participant reached stopping criteria
    0
    1
    2
    4
    3
        Physician decision
    1
    0
    0
    0
    0
        Withdrawal by subject
    1
    0
    1
    0
    0
    Notes
    [57] - Safety Population
    [58] - Safety Population
    [59] - Safety Population
    [60] - Safety Population
    [61] - Safety Population
    No statistical analyses for this end point

    Secondary: Number of participants with AEs and serious adverse events (SAEs)

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    End point title
    		 Number of participants with AEs and serious adverse events (SAEs) [62]
    End point description
    An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability, is a congenital anomaly/ birth effect, other situations and is associated with liver injury or impaired liver function. One participant was randomized to the placebo but erroneously received daprodustat 25mg and was included in the 25mg subset analysis group for all safety population analyses.
    End point type
    Secondary
    End point timeframe
    Up to Day 43
    Notes
    [62] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period.
    End point values
    		 Placebo Dapro 10 mg Dapro 15 mg Dapro 30 mg Dapro 25 mg
    Number of subjects analysed
    19 [63]
    20 [64]
    20 [65]
    22 [66]
    22 [67]
    Units: Participants
        Any AE
    10
    10
    6
    7
    7
        Any SAE
    4
    3
    2
    3
    1
    Notes
    [63] - Safety Population
    [64] - Safety Population
    [65] - Safety Population
    [66] - Safety Population
    [67] - Safety Population
    No statistical analyses for this end point

    Secondary: Sodium, potassium, glucose, calcium, phosphate levels in blood at indicated time points

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    End point title
    		 Sodium, potassium, glucose, calcium, phosphate levels in blood at indicated time points [68]
    End point description
    Serum sodium, potassium, glucose, corrected calcium and phosphate levels were assessed as a clinical chemistry laboratory parameter from Baseline up to follow up visit at Day 43. Day 1 values were considered as Baseline values. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). One participant was randomized to the placebo but erroneously received daprodustat 25mg and was included in the 25mg subset analysis group for all safety population analyses.
    End point type
    Secondary
    End point timeframe
    Up to Day 43
    Notes
    [68] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period.
    End point values
    		 Placebo Dapro 10 mg Dapro 15 mg Dapro 30 mg Dapro 25 mg
    Number of subjects analysed
    19 [69]
    20 [70]
    20 [71]
    22 [72]
    22 [73]
    Units: Millimoles per liter (mmol/L)
    arithmetic mean (standard deviation)
        Sodium; Day 1; n= 18, 20, 20, 22, 22
    138.8 ( 2.85 )
    138.1 ( 2.31 )
    138.7 ( 2.83 )
    138.4 ( 1.76 )
    139.4 ( 2.38 )
        Sodium; Day 15; n= 17, 20, 18, 20, 22
    137.7 ( 3.16 )
    137.5 ( 2.72 )
    138.1 ( 1.60 )
    137.2 ( 1.74 )
    138.0 ( 2.36 )
        Sodium; Day 29; n= 17, 19, 18, 17, 19
    137.8 ( 3.96 )
    136.8 ( 2.70 )
    137.9 ( 2.85 )
    137.1 ( 2.46 )
    138.8 ( 2.74 )
        Sodium; Day 43; n= 15, 20, 18, 21, 21
    139.2 ( 2.88 )
    138.1 ( 1.77 )
    137.9 ( 2.37 )
    137.6 ( 1.88 )
    138.8 ( 2.02 )
        Potassium; Day 1; n= 18, 20, 20, 22, 22
    4.68 ( 0.840 )
    4.73 ( 0.768 )
    4.64 ( 0.826 )
    4.83 ( 0.685 )
    4.79 ( 0.514 )
        Potassium; Day 15; n= 17, 20, 18, 20, 22
    4.72 ( 0.763 )
    4.77 ( 0.542 )
    4.57 ( 0.635 )
    4.80 ( 0.791 )
    4.82 ( 0.765 )
        Potassium; Day 29; n= 17, 19, 18, 17, 19
    4.78 ( 0.919 )
    4.87 ( 0.751 )
    4.57 ( 0.472 )
    4.96 ( 0.941 )
    4.86 ( 0.619 )
        Potassium; Day 43; n= 15, 20, 18, 21, 21
    4.69 ( 0.951 )
    4.68 ( 0.562 )
    4.59 ( 0.657 )
    4.80 ( 0.946 )
    4.76 ( 0.752 )
        Glucose; Day 1; n= 18, 20, 20, 22, 22
    6.66 ( 3.088 )
    6.66 ( 2.716 )
    6.41 ( 3.507 )
    8.95 ( 5.012 )
    7.05 ( 2.491 )
        Glucose; Day 15; n= 17, 20, 18, 20, 22
    7.89 ( 3.425 )
    7.16 ( 2.844 )
    7.03 ( 3.236 )
    8.67 ( 4.198 )
    7.26 ( 2.852 )
        Glucose; Day 29; n= 17, 19, 18, 17, 19
    8.21 ( 4.951 )
    7.49 ( 3.949 )
    7.21 ( 3.953 )
    8.75 ( 5.708 )
    7.77 ( 4.621 )
        Glucose; Day 43; n= 15, 20, 18, 21, 21
    6.93 ( 3.126 )
    6.72 ( 2.965 )
    7.09 ( 3.533 )
    8.93 ( 4.280 )
    6.27 ( 1.958 )
        Calcium corrected; Day 1; n= 18, 20, 20, 22, 22
    2.286 ( 0.2116 )
    2.270 ( 0.1244 )
    2.241 ( 0.1675 )
    2.215 ( 0.1163 )
    2.219 ( 0.1589 )
        Calcium corrected; Day 15; n= 17, 20, 18, 20, 22
    2.261 ( 0.1698 )
    2.219 ( 0.1252 )
    2.213 ( 0.1723 )
    2.203 ( 0.1111 )
    2.188 ( 0.1360 )
        Calcium corrected; Day 29; n= 17, 19, 18, 17, 19
    2.205 ( 0.1431 )
    2.248 ( 0.1352 )
    2.244 ( 0.1577 )
    2.225 ( 0.1810 )
    2.198 ( 0.1343 )
        Calcium corrected; Day 43; n= 15, 20, 18, 21, 21
    2.251 ( 0.1582 )
    2.235 ( 0.1593 )
    2.271 ( 0.1823 )
    2.256 ( 0.1473 )
    2.201 ( 0.1206 )
        Phosphate; Day 1; n= 18, 20, 20, 22, 22
    1.608 ( 0.5143 )
    1.528 ( 0.5557 )
    1.498 ( 0.5265 )
    1.566 ( 0.4269 )
    1.318 ( 0.3647 )
        Phosphate; Day 15; n= 17, 20, 18, 20. 22
    1.621 ( 0.4221 )
    1.710 ( 0.3912 )
    1.642 ( 0.5021 )
    1.645 ( 0.4785 )
    1.348 ( 0.3138 )
        Phosphate; Day 29; n= 17, 19, 18, 17, 19
    1.709 ( 0.5872 )
    1.592 ( 0.4121 )
    1.644 ( 0.5322 )
    1.550 ( 0.3575 )
    1.453 ( 0.4489 )
        Phosphate; Day 43; n= 15, 20, 18, 21, 21
    1.550 ( 0.5828 )
    1.460 ( 0.4550 )
    1.472 ( 0.4240 )
    1.398 ( 0.4718 )
    1.412 ( 0.4441 )
    Notes
    [69] - Safety Population
    [70] - Safety Population
    [71] - Safety Population
    [72] - Safety Population
    [73] - Safety Population
    No statistical analyses for this end point

    Secondary: Albumin and protein levels in blood at indicated tme points

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    End point title
    		 Albumin and protein levels in blood at indicated tme points [74]
    End point description
    Serum albumin and protein levels were assessed as a clinical chemistry laboratory parameter from Baseline up to follow up visit at Day 43. Day 1 values were considered as Baseline values. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). One participant was randomized to the placebo but erroneously received daprodustat 25mg and was included in the 25mg subset analysis group for all safety population analyses.
    End point type
    Secondary
    End point timeframe
    Up to Day 43
    Notes
    [74] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period.
    End point values
    		 Placebo Dapro 10 mg Dapro 15 mg Dapro 30 mg Dapro 25 mg
    Number of subjects analysed
    19 [75]
    20 [76]
    20 [77]
    22 [78]
    22 [79]
    Units: grams per liter (g/L)
    arithmetic mean (standard deviation)
        Albumin; Day 1; n= 18, 20, 20, 22, 22
    37.6 ( 2.89 )
    38.6 ( 2.46 )
    38.7 ( 3.84 )
    38.1 ( 3.52 )
    38.8 ( 2.22 )
        Albumin; Day 15; n= 17, 20, 18, 20, 22
    38.1 ( 2.68 )
    38.1 ( 2.65 )
    38.4 ( 3.42 )
    37.2 ( 3.01 )
    38.4 ( 2.52 )
        Albumin; Day 29; n= 17, 19, 18, 17, 19
    36.5 ( 3.22 )
    37.2 ( 3.26 )
    37.6 ( 3.62 )
    36.9 ( 4.15 )
    37.4 ( 2.17 )
        Albumin; Day 43; n= 15, 20, 18, 21, 21
    37.1 ( 2.85 )
    38.1 ( 3.02 )
    37.9 ( 3.95 )
    37.5 ( 2.86 )
    39.0 ( 3.11 )
        Protein; Day 1; n= 18, 20 ,20, 22, 22
    67.3 ( 4.90 )
    66.9 ( 5.42 )
    67.4 ( 4.89 )
    65.7 ( 4.65 )
    66.4 ( 5.16 )
        Protein; Day 15; n= 17, 20, 18, 20, 22
    68.1 ( 4.87 )
    66.5 ( 4.88 )
    67.3 ( 4.28 )
    64.3 ( 4.70 )
    65.6 ( 5.13 )
        Protein; Day 29; n= 17, 19, 18, 17, 19
    66.1 ( 4.52 )
    65.7 ( 4.75 )
    66.0 ( 4.51 )
    65.3 ( 5.30 )
    65.5 ( 6.50 )
        Protein; Day 43; n= 15, 20, 18, 21, 21
    67.2 ( 4.25 )
    67.4 ( 5.14 )
    66.8 ( 4.02 )
    66.6 ( 6.34 )
    66.7 ( 7.70 )
    Notes
    [75] - Safety Population
    [76] - Safety Population
    [77] - Safety Population
    [78] - Safety Population
    [79] - Safety Population
    No statistical analyses for this end point

    Secondary: Alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (alk. phosph) levels in blood at indicated time points

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    End point title
    		 Alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (alk. phosph) levels in blood at indicated time points [80]
    End point description
    Serum ALT, AST and alk. phosph. levels were assessed as a clinical chemistry laboratory parameter from Baseline up to follow up visit at Day 43. Day 1 values were considered as Baseline values. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). One participant was randomized to the placebo but erroneously received daprodustat 25mg and was included in the 25mg subset analysis group for all safety population analyses.
    End point type
    Secondary
    End point timeframe
    Up to Day 43
    Notes
    [80] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period.
    End point values
    		 Placebo Dapro 10 mg Dapro 15 mg Dapro 30 mg Dapro 25 mg
    Number of subjects analysed
    19 [81]
    20 [82]
    20 [83]
    22 [84]
    22 [85]
    Units: IU/L
    arithmetic mean (standard deviation)
        ALT; Day 1; n= 18, 20, 20, 22, 22
    12.6 ( 9.36 )
    13.4 ( 7.51 )
    14.6 ( 11.39 )
    11.5 ( 5.94 )
    10.7 ( 5.75 )
        ALT; Day 15; n= 17, 20, 18, 20, 22
    16.5 ( 13.80 )
    13.9 ( 10.58 )
    12.4 ( 7.87 )
    8.4 ( 2.11 )
    11.9 ( 6.58 )
        ALT; Day 29; n= 17, 19, 18, 17, 19
    24.4 ( 32.34 )
    12.8 ( 6.43 )
    12.2 ( 6.40 )
    8.6 ( 3.12 )
    10.9 ( 5.67 )
        ALT; Day 43; n= 15, 20, 18, 21, 21
    14.3 ( 8.55 )
    13.8 ( 8.03 )
    12.8 ( 6.89 )
    11.2 ( 5.57 )
    13.1 ( 5.19 )
        AST; Day 1; n= 18, 20, 20, 22, 22
    14.9 ( 5.58 )
    14.2 ( 5.19 )
    17.2 ( 12.31 )
    13.6 ( 3.63 )
    14.4 ( 5.85 )
        AST; Day 15; n= 17, 20, 18, 20, 22
    17.1 ( 7.30 )
    14.3 ( 5.67 )
    15.0 ( 7.72 )
    12.4 ( 2.89 )
    15.4 ( 6.33 )
        AST; Day 29; n= 17, 19, 18, 17, 19
    26.8 ( 30.04 )
    13.8 ( 5.01 )
    16.0 ( 8.44 )
    13.5 ( 3.12 )
    15.0 ( 6.35 )
        AST; Day 43; n= 15, 20, 18, 21, 21
    15.9 ( 6.65 )
    14.9 ( 6.07 )
    17.2 ( 11.40 )
    14.3 ( 4.76 )
    15.7 ( 6.31 )
        Alk. phosph; Day 1; n= 18, 20, 20, 22, 22
    97.0 ( 33.07 )
    112.3 ( 74.61 )
    106.8 ( 84.85 )
    115.4 ( 72.35 )
    99.4 ( 47.26 )
        Alk. phosph; Day 15; n= 17, 20, 18, 20, 22
    102.4 ( 34.70 )
    115.4 ( 73.37 )
    114.5 ( 82.29 )
    110.0 ( 62.65 )
    101.5 ( 56.44 )
        Alk. phosph.; Day 29; n= 17, 19, 18, 17, 19
    94.1 ( 35.07 )
    120.2 ( 81.15 )
    109.2 ( 83.14 )
    120.4 ( 67.51 )
    93.5 ( 42.92 )
        Alk. phosph.; Day 43; n= 15, 20, 18, 21,21
    96.5 ( 34.12 )
    117.6 ( 76.61 )
    113.8 ( 78.69 )
    108.6 ( 50.49 )
    116.2 ( 96.02 )
    Notes
    [81] - Safety Population
    [82] - Safety Population
    [83] - Safety Population
    [84] - Safety Population
    [85] - Safety Population
    No statistical analyses for this end point

    Secondary: Bilirubin, direct bilirubin and indirect bilirubin levels in blood at indicated time points

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    End point title
    		 Bilirubin, direct bilirubin and indirect bilirubin levels in blood at indicated time points [86]
    End point description
    Serum bilirubin, direct bilirubin and indirect bilirubin levels were assessed as a clinical chemistry laboratory parameter from Baseline up to follow up visit at Day 43. Day 1 values were considered as Baseline values. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). One participant was randomized to the placebo but erroneously received daprodustat 25mg and was included in the 25mg subset analysis group for all safety population analyses.
    End point type
    Secondary
    End point timeframe
    Up to Day 43
    Notes
    [86] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period.
    End point values
    		 Placebo Dapro 10 mg Dapro 15 mg Dapro 30 mg Dapro 25 mg
    Number of subjects analysed
    19 [87]
    20 [88]
    20 [89]
    22 [90]
    22 [91]
    Units: Micromoles per liter (µmol/L)
    arithmetic mean (standard deviation)
        Bilirubin; Day 1; n= 18, 20, 20, 22, 22
    6.6 ( 1.65 )
    7.8 ( 3.11 )
    6.6 ( 1.31 )
    7.2 ( 2.44 )
    6.5 ( 1.10 )
        Bilirubin; Day 15; n= 17, 20, 18, 20, 22
    6.7 ( 3.08 )
    7.1 ( 2.29 )
    7.2 ( 2.67 )
    7.8 ( 2.24 )
    6.5 ( 1.10 )
        Bilirubin; Day 29; n= 17, 19, 18, 17, 19
    6.8 ( 2.24 )
    6.9 ( 1.93 )
    7.6 ( 2.12 )
    7.8 ( 2.44 )
    6.5 ( 1.47 )
        Bilirubin; Day 43; n= 15, 20 ,18, 21, 21
    6.0 ( 1.07 )
    7.0 ( 2.38 )
    7.2 ( 2.07 )
    7.5 ( 2.44 )
    6.5 ( 1.25 )
        Direct bilirubin; Day 1; n= 18, 20, 20, 22, 22
    1.8 ( 1.17 )
    1.9 ( 0.79 )
    2.0 ( 1.12 )
    2.4 ( 1.33 )
    1.9 ( 0.75 )
        Direct bilirubin; Day 15; n= 17, 20, 18, 20, 22
    1.5 ( 1.66 )
    2.2 ( 0.62 )
    2.4 ( 1.29 )
    2.6 ( 1.14 )
    1.8 ( 0.85 )
        Direct bilirubin; Day 29; n= 17, 19, 18, 17, 19
    2.5 ( 2.29 )
    1.6 ( 1.07 )
    2.7 ( 0.97 )
    2.4 ( 1.46 )
    1.8 ( 0.63 )
        Direct bilirubin; Day 43; n= 15, 20, 18, 21,21
    1.3 ( 1.23 )
    1.9 ( 0.45 )
    2.3 ( 0.77 )
    2.3 ( 1.31 )
    1.7 ( 0.72 )
        Indirect bilirubin; Day 1; n= 18, 20, 20, 22, 22
    4.8 ( 1.22 )
    5.9 ( 2.94 )
    4.6 ( 0.94 )
    4.8 ( 1.92 )
    4.6 ( 1.14 )
        Indirect bilirubin; Day 15; n= 17, 20, 18, 20, 22
    5.2 ( 2.01 )
    4.9 ( 2.10 )
    4.8 ( 1.83 )
    5.2 ( 1.77 )
    4.7 ( 0.98 )
        Indirect bilirubin; Day 29; n= 17, 19, 18, 17, 19
    4.4 ( 2.03 )
    5.4 ( 1.64 )
    4.9 ( 1.57 )
    5.4 ( 1.70 )
    4.7 ( 1.52 )
        Indirect bilirubin; Day 43; n= 15, 20, 18, 21, 21
    4.7 ( 0.98 )
    5.1 ( 2.38 )
    4.9 ( 1.41 )
    5.2 ( 1.73 )
    4.8 ( 1.48 )
    Notes
    [87] - Safety Population
    [88] - Safety Population
    [89] - Safety Population
    [90] - Safety Population
    [91] - Safety Population
    No statistical analyses for this end point

    Secondary: Change from Baseline in sodium, potassium, glucose, calcium and phosphate levels

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    End point title
    		 Change from Baseline in sodium, potassium, glucose, calcium and phosphate levels [92]
    End point description
    Blood samples were collected from participants to evaluate clinical chemistry parameters including sodium, potassium, glucose, calcium and phosphate. Change from Baseline in clinical chemistry parameters at Day 15, Day 29 and Day 43 are presented. Day 1 values were considered as Baseline values. Change from Baseline was calculated by subtracting post-Baseline visit values minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). One participant was randomized to the placebo but erroneously received daprodustat 25mg and was included in the 25mg subset analysis group for all safety population analyses.
    End point type
    Secondary
    End point timeframe
    Baseline and up to Day 43
    Notes
    [92] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period.
    End point values
    		 Placebo Dapro 10 mg Dapro 15 mg Dapro 30 mg Dapro 25 mg
    Number of subjects analysed
    19 [93]
    20 [94]
    20 [95]
    22 [96]
    22 [97]
    Units: Mmol/L
    arithmetic mean (standard deviation)
        Sodium; Day 15; n= 17, 20, 18, 20, 22
    -0.9 ( 2.73 )
    -0.6 ( 2.62 )
    -0.5 ( 2.64 )
    -1.0 ( 2.13 )
    -1.4 ( 2.06 )
        Sodium; Day 29; n= 17, 19, 18, 17, 19
    -1.1 ( 2.26 )
    -1.2 ( 3.08 )
    -0.9 ( 2.26 )
    -1.2 ( 2.70 )
    -0.5 ( 2.82 )
        Sodium; Day 43; n= 15, 20, 18, 21, 21
    0.7 ( 2.06 )
    0.1 ( 2.35 )
    -0.6 ( 2.28 )
    -0.6 ( 2.23 )
    -0.5 ( 2.60 )
        Potassium; Day 15; n= 17, 20, 18, 20, 22
    0.04 ( 0.462 )
    0.05 ( 0.526 )
    -0.09 ( 1.099 )
    -0.08 ( 0.635 )
    0.03 ( 0.944 )
        Potassium; Day 29; n= 17, 19, 18, 17, 19
    0.20 ( 0.744 )
    0.05 ( 0.660 )
    -0.14 ( 0.651 )
    0.11 ( 0.673 )
    0.02 ( 0.640 )
        Potassium; Day 43; n= 15, 20, 18, 21, 21
    0.04 ( 0.565 )
    -0.05 ( 0.674 )
    -0.06 ( 1.004 )
    -0.02 ( 0.932 )
    -0.06 ( 0.579 )
        Glucose; Day 15; n= 17, 20, 18, 20, 22
    1.14 ( 3.339 )
    0.51 ( 2.959 )
    0.45 ( 1.740 )
    -0.03 ( 2.364 )
    0.21 ( 1.620 )
        Glucose; Day 29; n= 17, 19, 18, 17, 19
    1.48 ( 3.771 )
    0.70 ( 3.756 )
    0.73 ( 1.135 )
    -0.36 ( 3.786 )
    0.61 ( 4.188 )
        Glucose; Day 43; n= 15, 20, 18, 21, 21
    0.23 ( 1.335 )
    0.06 ( 3.072 )
    0.52 ( 1.383 )
    -0.12 ( 3.619 )
    -0.81 ( 2.516 )
        Calcium; Day 15; n= 17, 20, 18, 20, 22
    -0.011 ( 0.1227 )
    -0.051 ( 0.1354 )
    -0.026 ( 0.1439 )
    -0.010 ( 0.0912 )
    -0.031 ( 0.0956 )
        Calcium; Day 29; n= 17, 19, 18, 17, 19
    -0.054 ( 0.1486 )
    -0.025 ( 0.1129 )
    -0.009 ( 0.1556 )
    0.001 ( 0.1019 )
    -0.012 ( 0.0939 )
        Calcium; Day 43; n= 15, 20, 18, 21, 21
    -0.015 ( 0.1576 )
    -0.035 ( 0.1261 )
    0.018 ( 0.1852 )
    0.033 ( 0.1489 )
    0.001 ( 0.0742 )
        Phosphate; Day 15; n= 17, 20, 18, 20, 22
    -0.091 ( 0.4051 )
    0.183 ( 0.5184 )
    0.111 ( 0.5715 )
    0.095 ( 0.3367 )
    0.030 ( 0.3268 )
        Phosphate; Day 29; n= 17, 19, 18, 17, 19
    0.091 ( 0.3882 )
    0.011 ( 0.4932 )
    0.069 ( 0.4950 )
    -0.026 ( 0.3653 )
    0.129 ( 0.2740 )
        Phosphate; Day 43; n= 15, 20, 18, 21, 21
    -0.067 ( 0.4337 )
    -0.068 ( 0.5324 )
    -0.053 ( 0.5400 )
    -0.117 ( 0.5117 )
    0.102 ( 0.3433 )
    Notes
    [93] - Safety Population
    [94] - Safety Population
    [95] - Safety Population
    [96] - Safety Population
    [97] - Safety Population
    No statistical analyses for this end point

    Secondary: Change from Baseline in albumin and protein levels

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    End point title
    		 Change from Baseline in albumin and protein levels [98]
    End point description
    Blood samples were collected from participants to evaluate clinical chemistry parameters including albumin and protein. Change from Baseline in clinical chemistry parameters at Day 15, Day 29 and Day 43 are presented. Day 1 values were considered as Baseline values. Change from Baseline was calculated by subtracting post-Baseline visit values minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). One participant was randomized to the placebo but erroneously received daprodustat 25mg and was included in the 25mg subset analysis group for all safety population analyses.
    End point type
    Secondary
    End point timeframe
    Baseline and up to Day 43
    Notes
    [98] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period.
    End point values
    		 Placebo Dapro 10 mg Dapro 15 mg Dapro 30 mg Dapro 25 mg
    Number of subjects analysed
    19 [99]
    20 [100]
    20 [101]
    22 [102]
    22 [103]
    Units: g/L
    arithmetic mean (standard deviation)
        Albumin; Day 15; n= 17, 20, 18, 20, 22
    0.8 ( 1.60 )
    -0.5 ( 1.64 )
    0.2 ( 2.24 )
    -1.0 ( 2.34 )
    -0.5 ( 1.44 )
        Albumin; Day 29; n= 17, 19, 18, 17, 19
    -0.5 ( 2.24 )
    -1.3 ( 2.03 )
    -0.7 ( 2.00 )
    -0.9 ( 1.76 )
    -1.3 ( 1.85 )
        Albumin; Day 43; n= 15, 20, 18, 21, 21
    0.1 ( 2.00 )
    -0.6 ( 2.14 )
    -0.7 ( 2.22 )
    -0.3 ( 1.74 )
    0.1 ( 3.85 )
        Protein; Day 15; n= 17, 20, 18, 20, 22
    0.8 ( 2.97 )
    -0.4 ( 3.25 )
    0.3 ( 3.65 )
    -1.5 ( 3.03 )
    -0.7 ( 2.35 )
        Protein; Day 29; n= 17, 19, 18, 17, 19
    -1.1 ( 4.26 )
    -0.8 ( 3.82 )
    -1.2 ( 2.90 )
    0.1 ( 2.56 )
    -1.0 ( 3.28 )
        Protein; Day 43; n= 15, 20, 18, 21, 21
    -0.1 ( 4.19 )
    0.6 ( 4.38 )
    -0.9 ( 3.17 )
    1.2 ( 3.95 )
    0.3 ( 4.84 )
    Notes
    [99] - Safety Population
    [100] - Safety Population
    [101] - Safety Population
    [102] - Safety Population
    [103] - Safety Population
    No statistical analyses for this end point

    Secondary: Change from Baseline in ALT, AST, Alk. phosph. levels

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    End point title
    		 Change from Baseline in ALT, AST, Alk. phosph. levels [104]
    End point description
    Blood samples were collected from participants to evaluate clinical chemistry parameters including ALT, AST, Alk. phosph. Change from Baseline in clinical chemistry parameters at Day 15, Day 29 and Day 43 are presented. Day 1 values were considered as Baseline values. Change from Baseline was calculated by subtracting post-Baseline visit values minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). One participant was randomized to the placebo but erroneously received daprodustat 25mg and was included in the 25mg subset analysis group for all safety population analyses.
    End point type
    Secondary
    End point timeframe
    Baseline and up to Day 43
    Notes
    [104] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period.
    End point values
    		 Placebo Dapro 10 mg Dapro 15 mg Dapro 30 mg Dapro 25 mg
    Number of subjects analysed
    19 [105]
    20 [106]
    20 [107]
    22 [108]
    22 [109]
    Units: IU/L
    arithmetic mean (standard deviation)
        ALT; Day 15; n= 17, 20, 18, 20, 22
    3.6 ( 9.59 )
    0.5 ( 5.65 )
    -3.1 ( 5.53 )
    -3.4 ( 5.52 )
    1.1 ( 4.79 )
        ALT; Day 29; n= 17, 19, 18, 17, 19
    11.8 ( 32.39 )
    -0.9 ( 4.65 )
    -3.4 ( 9.83 )
    -3.6 ( 4.72 )
    -0.2 ( 3.87 )
        ALT; Day 43; n= 15, 20, 18, 21, 21
    0.9 ( 4.32 )
    0.4 ( 5.29 )
    -2.5 ( 8.97 )
    -0.4 ( 3.69 )
    2.2 ( 4.08 )
        AST; Day 15; n= 17, 20, 18, 20, 22
    2.3 ( 5.70 )
    0.1 ( 2.45 )
    -2.7 ( 6.29 )
    -1.6 ( 3.32 )
    1.0 ( 5.26 )
        AST; Day 29; n= 17, 19, 18, 17, 19
    11.5 ( 30.64 )
    -0.3 ( 3.30 )
    -1.8 ( 5.60 )
    -0.3 ( 3.67 )
    0.9 ( 3.60 )
        AST; Day 43; n= 15, 20, 18, 21, 21
    0.6 ( 3.94 )
    0.7 ( 2.49 )
    -0.6 ( 7.99 )
    0.7 ( 3.41 )
    1.5 ( 3.71 )
        Alk.phosph.; Day 15; n= 17, 20, 18, 20, 22
    3.2 ( 10.28 )
    3.2 ( 16.13 )
    2.7 ( 29.73 )
    -4.7 ( 18.90 )
    2.1 ( 17.23 )
        Alk.phosph.; Day 29; n= 17, 19, 18, 17, 19
    -0.4 ( 19.31 )
    5.1 ( 19.09 )
    -0.9 ( 30.13 )
    -1.2 ( 28.60 )
    0.9 ( 13.47 )
        Alk.phosph.; Day 43; n= 15, 20, 18, 21, 21
    -1.5 ( 17.01 )
    5.4 ( 21.34 )
    2.7 ( 31.96 )
    -8.4 ( 56.06 )
    18.0 ( 66.44 )
    Notes
    [105] - Safety Population
    [106] - Safety Population
    [107] - Safety Population
    [108] - Safety Population
    [109] - Safety Population
    No statistical analyses for this end point

    Secondary: Change from Baseline in bilirubin, direct bilirubin, indirect bilirubin levels

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    End point title
    		 Change from Baseline in bilirubin, direct bilirubin, indirect bilirubin levels [110]
    End point description
    Blood samples were collected from participants to evaluate clinical chemistry parameters including bilirubin, direct bilirubin and indirect bilirubin. Change from Baseline in clinical chemistry parameters at Day 15, Day 29 and Day 43 are presented. Day 1 values were considered as Baseline values. Change from Baseline was calculated by subtracting post-Baseline visit values minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). One participant was randomized to the placebo but erroneously received daprodustat 25mg and was included in the 25mg subset analysis group for all safety population analyses.
    End point type
    Secondary
    End point timeframe
    Baseline and up to Day 43
    Notes
    [110] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period.
    End point values
    		 Placebo Dapro 10 mg Dapro 15 mg Dapro 30 mg Dapro 25 mg
    Number of subjects analysed
    19 [111]
    20 [112]
    20 [113]
    22 [114]
    22 [115]
    Units: µmol/L
    arithmetic mean (standard deviation)
        Bilirubin; Day 15; n= 17, 20, 18, 20, 22
    0.2 ( 1.56 )
    -0.7 ( 1.49 )
    0.8 ( 2.07 )
    0.5 ( 1.93 )
    0.0 ( 1.38 )
        Bilirubin; Day 29; n= 17, 19, 18, 17, 19
    0.2 ( 0.97 )
    -0.3 ( 1.20 )
    1.0 ( 1.41 )
    0.2 ( 0.97 )
    0.1 ( 1.56 )
        Bilirubin; Day 43; n= 15, 20, 18, 21, 21
    -0.1 ( 0.52 )
    -0.8 ( 1.51 )
    0.6 ( 2.04 )
    0.4 ( 1.36 )
    0.1 ( 1.34 )
        Direct bilirubin; Day 15; n= 17, 20, 18, 20, 22
    -0.1 ( 1.11 )
    0.3 ( 0.73 )
    0.6 ( 0.92 )
    0.2 ( 1.11 )
    -0.1 ( 0.97 )
        Direct bilirubin; Day 29; n= 17, 19, 18, 17, 19
    0.7 ( 1.86 )
    -0.3 ( 1.00 )
    0.7 ( 0.97 )
    -0.1 ( 1.50 )
    -0.1 ( 1.05 )
        Direct bilirubin; Day 43; n= 15, 20, 18, 21, 21
    -0.1 ( 1.19 )
    0.0 ( 0.92 )
    0.3 ( 1.03 )
    -0.1 ( 1.34 )
    -0.2 ( 1.08 )
        Indirect bilirubin; Day 15; n= 17, 20, 18, 20, 22
    0.4 ( 1.46 )
    -1.0 ( 1.38 )
    0.2 ( 1.80 )
    0.3 ( 1.75 )
    0.1 ( 1.44 )
        Indirect bilirubin; Day 29; n= 17, 19, 18, 17, 19
    -0.5 ( 1.66 )
    0.0 ( 1.15 )
    0.3 ( 1.71 )
    0.4 ( 1.46 )
    0.2 ( 1.62 )
        Indirect bilirubin; Day 43; n= 15, 20, 18, 21, 21
    0.0 ( 1.07 )
    -0.8 ( 1.64 )
    0.2 ( 1.66 )
    0.5 ( 1.40 )
    0.3 ( 1.82 )
    Notes
    [111] - Safety Population
    [112] - Safety Population
    [113] - Safety Population
    [114] - Safety Population
    [115] - Safety Population
    No statistical analyses for this end point

    Secondary: Leukocytes, neutrophils, basophils, eosinophils,lymphocytes, monocytes, platelet levels in blood at indicated time points

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    End point title
    		 Leukocytes, neutrophils, basophils, eosinophils,lymphocytes, monocytes, platelet levels in blood at indicated time points [116]
    End point description
    Serum leukocytes, neutrophils, basophils, eosinophils, lymphocytes, monocytes and platelet levels were assessed as a clinical hematology laboratory parameter from Baseline up to follow up visit at Day 43. Day 1 values were considered as Baseline values. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).One participant was randomized to the placebo but erroneously received daprodustat 25mg and was included in the 25mg subset analysis group for all safety population analyses.
    End point type
    Secondary
    End point timeframe
    Up to Day 43
    Notes
    [116] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period.
    End point values
    		 Placebo Dapro 10 mg Dapro 15 mg Dapro 30 mg Dapro 25 mg
    Number of subjects analysed
    19 [117]
    20 [118]
    20 [119]
    22 [120]
    22 [121]
    Units: 10^12 cells/L
    arithmetic mean (standard deviation)
        Leukocytes; Day 1; n= 18, 19, 19, 21, 20
    6.28 ( 1.750 )
    6.07 ( 1.601 )
    5.88 ( 1.510 )
    5.90 ( 1.825 )
    6.44 ( 1.595 )
        Leukocytes; Day 15; n= 17, 19, 17, 21, 21
    7.01 ( 2.140 )
    5.85 ( 1.720 )
    6.21 ( 1.918 )
    5.87 ( 1.961 )
    6.52 ( 1.427 )
        Leukocytes; Day 29; n= 16, 19, 17, 17, 18
    6.66 ( 1.707 )
    6.59 ( 1.890 )
    5.88 ( 1.685 )
    6.11 ( 2.574 )
    6.33 ( 1.820 )
        Leukocytes; Day 43; n= 16, 20, 19, 19, 20
    7.05 ( 2.006 )
    7.25 ( 2.520 )
    6.00 ( 1.694 )
    6.42 ( 2.010 )
    6.77 ( 2.547 )
        Neutrophils; Day 1; n= 18, 19, 19, 21, 20
    4.030 ( 1.6128 )
    4.097 ( 1.5763 )
    3.522 ( 1.3492 )
    3.785 ( 1.5024 )
    3.954 ( 1.4097 )
        Neutrophils; Day 15; n= 17, 19, 17, 21, 21
    4.666 ( 1.8113 )
    3.887 ( 1.5659 )
    3.707 ( 1.6592 )
    4.129 ( 1.6604 )
    4.346 ( 1.2240 )
        Neutrophils; Day 29; n= 16, 18, 17, 15, 17
    4.123 ( 1.2229 )
    4.591 ( 1.9586 )
    3.522 ( 1.4546 )
    4.224 ( 2.2017 )
    3.978 ( 1.7026 )
        Neutrophils; Day 43; n= 16, 20, 19, 19, 19
    4.687 ( 1.8919 )
    5.049 ( 2.3848 )
    3.545 ( 1.4027 )
    4.343 ( 1.6235 )
    4.477 ( 2.2480 )
        Basophils; Day 1; n= 18, 19, 19, 21, 20
    0.018 ( 0.0131 )
    0.016 ( 0.0134 )
    0.025 ( 0.0174 )
    0.017 ( 0.0142 )
    0.028 ( 0.0204 )
        Basophils; Day 15; n= 17, 19, 17, 21, 21
    0.027 ( 0.0214 )
    0.026 ( 0.0161 )
    0.022 ( 0.0139 )
    0.024 ( 0.0140 )
    0.025 ( 0.0325 )
        Basophils; Day 29; n= 16, 18, 17, 15, 17
    0.035 ( 0.0462 )
    0.021 ( 0.0128 )
    0.021 ( 0.0150 )
    0.027 ( 0.0315 )
    0.024 ( 0.0111 )
        Basophils; Day 43; n= 16, 20, 19, 19, 19
    0.028 ( 0.0217 )
    0.018 ( 0.0136 )
    0.020 ( 0.0183 )
    0.024 ( 0.0130 )
    0.025 ( 0.0204 )
        Eosinophils; Day 1; n= 18, 19, 19, 21, 20
    0.189 ( 0.1946 )
    0.174 ( 0.1593 )
    0.184 ( 0.1696 )
    0.240 ( 0.2115 )
    0.196 ( 0.2310 )
        Eosinophils; Day 15; n= 17, 19, 17, 21, 21
    0.161 ( 0.1245 )
    0.166 ( 0.1804 )
    0.192 ( 0.2355 )
    0.186 ( 0.1914 )
    0.187 ( 0.2186 )
        Eosinophils; Day 29; n= 16, 18, 17, 15, 17
    0.176 ( 0.1917 )
    0.149 ( 0.0950 )
    0.145 ( 0.1136 )
    0.185 ( 0.0798 )
    0.237 ( 0.2785 )
        Eosinophils; Day 43; n= 16, 20, 19, 19, 19
    0.216 ( 0.2458 )
    0.210 ( 0.1969 )
    0.232 ( 0.2727 )
    0.217 ( 0.1899 )
    0.243 ( 0.2670 )
        Lymphocytes; Day 1; n= 18, 19, 19, 21, 20
    1.631 ( 0.4264 )
    1.393 ( 0.4587 )
    1.739 ( 0.6964 )
    1.442 ( 0.4998 )
    1.747 ( 0.7325 )
        Lymphocytes; Day 15; n= 17, 19, 17, 21, 21
    1.735 ( 0.6699 )
    1.416 ( 0.5670 )
    1.842 ( 0.7381 )
    1.206 ( 0.4609 )
    1.526 ( 0.6697 )
        Lymphocytes; Day 29; n= 16, 18, 17, 15, 17
    1.870 ( 0.7427 )
    1.427 ( 0.4187 )
    1.775 ( 0.6767 )
    1.181 ( 0.3418 )
    1.612 ( 0.5775 )
        Lymphocytes; Day 43; n= 16, 20, 19, 19, 19
    1.648 ( 0.5294 )
    1.509 ( 0.4386 )
    1.736 ( 0.3916 )
    1.399 ( 0.5562 )
    1.721 ( 0.6644 )
        Monocytes; Day 1; n= 18, 19, 20, 21, 20
    0.401 ( 0.1511 )
    0.396 ( 0.1591 )
    0.435 ( 0.2703 )
    0.421 ( 0.1722 )
    0.518 ( 0.2077 )
        Monocytes; Day 15; n= 17, 19, 17, 21, 21
    0.420 ( 0.2243 )
    0.352 ( 0.1457 )
    0.436 ( 0.2402 )
    0.384 ( 0.2160 )
    0.446 ( 0.2085 )
        Monocytes; Day 29; n= 16, 18, 17, 15, 17
    0.444 ( 0.2076 )
    0.457 ( 0.1503 )
    0.403 ( 0.1385 )
    0.426 ( 0.2628 )
    0.600 ( 0.3465 )
        Monocytes; Day 43; n= 16, 20, 19, 19, 19
    0.461 ( 0.1878 )
    0.459 ( 0.1916 )
    0.461 ( 0.2614 )
    0.429 ( 0.2047 )
    0.513 ( 0.2739 )
        Platelet; Day 1; n= 16, 19, 20, 21, 19
    219.0 ( 65.04 )
    189.9 ( 36.70 )
    198.0 ( 71.03 )
    192.3 ( 70.85 )
    196.0 ( 61.12 )
        Platelet; Day 15; n= 17, 18, 17, 21, 20
    205.4 ( 63.00 )
    175.4 ( 44.08 )
    198.5 ( 73.65 )
    181.5 ( 66.59 )
    194.8 ( 49.08 )
        Platelet; Day 29; n= 16, 19, 17, 17, 17
    198.1 ( 76.39 )
    174.7 ( 52.50 )
    187.5 ( 62.66 )
    194.8 ( 81.57 )
    198.9 ( 55.07 )
        Platelet; Day 43; n= 15, 20, 19, 20, 21
    220.8 ( 61.57 )
    195.8 ( 68.33 )
    188.6 ( 69.28 )
    170.0 ( 44.61 )
    194.1 ( 50.35 )
    Notes
    [117] - Safety Population
    [118] - Safety Population
    [119] - Safety Population
    [120] - Safety Population
    [121] - Safety Population
    No statistical analyses for this end point

    Secondary: Mean corpuscular hemoglobin (MCH) levels in blood at indicated time points

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    End point title
    		 Mean corpuscular hemoglobin (MCH) levels in blood at indicated time points [122]
    End point description
    Serum MCH levels were assessed as a clinical hematology laboratory parameter from Baseline up to follow up visit at Day 43. Day 1 values were considered as Baseline values. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). One participant was randomized to the placebo but erroneously received daprodustat 25mg and was included in the 25mg subset analysis group for all safety population analyses.
    End point type
    Secondary
    End point timeframe
    Up to Day 43
    Notes
    [122] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period.
    End point values
    		 Placebo Dapro 10 mg Dapro 15 mg Dapro 30 mg Dapro 25 mg
    Number of subjects analysed
    19 [123]
    20 [124]
    20 [125]
    22 [126]
    22 [127]
    Units: Pg
    arithmetic mean (standard deviation)
        Day 1; n= 18, 19, 20, 21, 20
    31.19 ( 2.538 )
    30.95 ( 1.889 )
    30.19 ( 2.145 )
    31.46 ( 1.942 )
    30.70 ( 1.781 )
        Day 15; n= 17, 19, 17, 21, 21
    30.83 ( 2.100 )
    2.100 ( 1.866 )
    30.74 ( 1.476 )
    31.70 ( 2.315 )
    30.85 ( 1.619 )
        Day 29; n= 16, 19, 17, 17, 18
    30.97 ( 2.290 )
    31.60 ( 2.194 )
    30.56 ( 2.236 )
    31.68 ( 2.224 )
    31.16 ( 1.729 )
        Day 43; n= 16, 20, 19, 20, 21
    30.86 ( 1.992 )
    31.04 ( 1.870 )
    30.49 ( 2.155 )
    31.84 ( 2.143 )
    30.67 ( 1.846 )
    Notes
    [123] - Safety Population
    [124] - Safety Population
    [125] - Safety Population
    [126] - Safety Population
    [127] - Safety Population
    No statistical analyses for this end point

    Secondary: Mean corpuscular hemoglobin concentration (MCHC) levels in blood at indicated time points

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    End point title
    		 Mean corpuscular hemoglobin concentration (MCHC) levels in blood at indicated time points [128]
    End point description
    Serum MCHC levels were assessed as a clinical hematology laboratory parameter from Baseline up to follow up visit at Day 43. Day 1 values were considered as Baseline values. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). One participant was randomized to the placebo but erroneously received daprodustat 25mg and was included in the 25mg subset analysis group for all safety population analyses.
    End point type
    Secondary
    End point timeframe
    Up to Day 43
    Notes
    [128] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period.
    End point values
    		 Placebo Dapro 10 mg Dapro 15 mg Dapro 30 mg Dapro 25 mg
    Number of subjects analysed
    19 [129]
    20 [130]
    20 [131]
    22 [132]
    22 [133]
    Units: g/L
    arithmetic mean (standard deviation)
        Day 1; n= 18, 19, 20, 21, 20
    322.9 ( 13.39 )
    321.7 ( 12.61 )
    319.5 ( 15.36 )
    327.6 ( 12.65 )
    321.5 ( 12.91 )
        Day 15; n= 17, 19, 17, 21, 21
    321.5 ( 11.22 )
    324.0 ( 7.79 )
    324.8 ( 8.35 )
    322.7 ( 14.75 )
    318.3 ( 12.06 )
        Day 29; n= 16, 19, 17, 17, 18
    323.3 ( 14.90 )
    329.6 ( 12.61 )
    325.4 ( 10.25 )
    323.9 ( 11.73 )
    323.6 ( 8.61 )
        Day 43; n= 16, 20, 19, 20, 21
    321.9 ( 13.22 )
    325.2 ( 11.98 )
    325.5 ( 11.23 )
    327.0 ( 10.66 )
    321.0 ( 11.00 )
    Notes
    [129] - Safety Population
    [130] - Safety Population
    [131] - Safety Population
    [132] - Safety Population
    [133] - Safety Population
    No statistical analyses for this end point

    Secondary: Mean Corpuscular volume (MCV) levels in blood at indicated time points

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    End point title
    		 Mean Corpuscular volume (MCV) levels in blood at indicated time points [134]
    End point description
    Serum MCV levels were assessed as a clinical hematology laboratory parameter from Baseline up to follow up visit at Day 43. Day 1 values were considered as Baseline values. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). One participant was randomized to the placebo but erroneously received daprodustat 25mg and was included in the 25mg subset analysis group for all safety population analyses.
    End point type
    Secondary
    End point timeframe
    Up to Day 43
    Notes
    [134] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period.
    End point values
    		 Placebo Dapro 10 mg Dapro 15 mg Dapro 30 mg Dapro 25 mg
    Number of subjects analysed
    19 [135]
    20 [136]
    20 [137]
    22 [138]
    22 [139]
    Units: Femtoliter (fL)
    arithmetic mean (standard deviation)
        Day 1; n= 18, 19, 20, 21, 20
    96.7 ( 5.94 )
    96.4 ( 5.68 )
    94.7 ( 5.28 )
    96.1 ( 5.61 )
    95.7 ( 4.91 )
        Day 15; n= 17, 19, 17, 21, 21
    95.9 ( 6.02 )
    95.8 ( 6.27 )
    94.8 ( 4.53 )
    98.3 ( 5.57 )
    97.0 ( 6.41 )
        Day 29; n= 16, 19, 17, 17, 18
    95.8 ( 5.83 )
    95.9 ( 6.05 )
    94.1 ( 5.94 )
    97.8 ( 4.96 )
    96.3 ( 4.76 )
        Day 43; n= 16, 20, 19, 20, 21
    96.1 ( 5.91 )
    95.4 ( 5.08 )
    93.7 ( 6.09 )
    97.5 ( 5.98 )
    95.6 ( 5.27 )
    Notes
    [135] - Safety Population
    [136] - Safety Population
    [137] - Safety Population
    [138] - Safety Population
    [139] - Safety Population
    No statistical analyses for this end point

    Secondary: Erythrocyte distribution width levels in blood at indicated time points

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    End point title
    		 Erythrocyte distribution width levels in blood at indicated time points [140]
    End point description
    Erythrocyte distribution width levels were assessed as a clinical hematology laboratory parameter from Baseline up to follow up visit at Day 43. Day 1 values were considered as Baseline values. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). One participant was randomized to the placebo but erroneously received daprodustat 25mg and was included in the 25mg subset analysis group for all safety population analyses.
    End point type
    Secondary
    End point timeframe
    Up to Day 43
    Notes
    [140] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period.
    End point values
    		 Placebo Dapro 10 mg Dapro 15 mg Dapro 30 mg Dapro 25 mg
    Number of subjects analysed
    19 [141]
    20 [142]
    20 [143]
    22 [144]
    22 [145]
    Units: Percentage of width
    arithmetic mean (standard deviation)
        Day 1; n= 18, 19, 20, 21, 20
    15.13 ( 2.607 )
    16.40 ( 2.082 )
    15.41 ( 1.627 )
    15.68 ( 1.725 )
    15.81 ( 2.504 )
        Day 15; n= 17, 19, 17, 21, 21
    15.05 ( 2.088 )
    15.77 ( 1.569 )
    15.26 ( 1.197 )
    16.74 ( 1.912 )
    16.30 ( 2.331 )
        Day 29; n= 16, 19, 17, 17, 18
    15.15 ( 2.530 )
    15.69 ( 1.750 )
    15.36 ( 1.287 )
    16.23 ( 1.668 )
    15.76 ( 1.253 )
        Day 43; n= 16, 20, 19, 20, 21
    15.53 ( 2.866 )
    15.53 ( 2.018 )
    14.95 ( 1.269 )
    15.48 ( 1.389 )
    15.61 ( 1.297 )
    Notes
    [141] - Safety Population
    [142] - Safety Population
    [143] - Safety Population
    [144] - Safety Population
    [145] - Safety Population
    No statistical analyses for this end point

    Secondary: Change from Baseline in MCH levels

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    End point title
    		 Change from Baseline in MCH levels [146]
    End point description
    Blood samples were collected from participants to evaluate clinical hematology parameters including MCH. Change from Baseline in clinical hematology parameters at Day 15, Day 29, Day 43 are presented. Day 1 values were considered as Baseline values. Change from Baseline was calculated by subtracting post-Baseline visit values minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). One participant was randomized to the placebo but erroneously received daprodustat 25mg and was included in the 25mg subset analysis group for all safety population analyses.
    End point type
    Secondary
    End point timeframe
    Baseline and up to Day 43
    Notes
    [146] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period.
    End point values
    		 Placebo Dapro 10 mg Dapro 15 mg Dapro 30 mg Dapro 25 mg
    Number of subjects analysed
    19 [147]
    20 [148]
    20 [149]
    22 [150]
    22 [151]
    Units: Pg
    arithmetic mean (standard deviation)
        Day 15; n= 17, 19, 17, 21, 21
    0.16 ( 0.602 )
    0.19 ( 0.817 )
    0.27 ( 0.685 )
    0.25 ( 0.870 )
    0.16 ( 0.520 )
        Day 29; n= 16, 19, 17, 17, 18
    0.16 ( 0.982 )
    0.58 ( 1.185 )
    0.42 ( 0.824 )
    0.15 ( 0.987 )
    0.41 ( 0.744 )
        Day 43; n= 16, 20, 19, 20, 21
    0.11 ( 0.981 )
    0.13 ( 0.948 )
    0.34 ( 0.993 )
    0.29 ( 0.809 )
    0.11 ( 0.842 )
    Notes
    [147] - Safety Population
    [148] - Safety Population
    [149] - Safety Population
    [150] - Safety Population
    [151] - Safety Population
    No statistical analyses for this end point

    Secondary: Change from Baseline in MCHC levels

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    End point title
    		 Change from Baseline in MCHC levels [152]
    End point description
    Blood samples were collected from participants to evaluate clinical hematology parameters including MCHC. Change from Baseline in clinical hematology parameters at Day 15, Day 29, Day 43 are presented. Day 1 values were considered as Baseline values. Change from Baseline was calculated by subtracting post-Baseline visit values minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). One participant was randomized to the placebo but erroneously received daprodustat 25mg and was included in the 25mg subset analysis group for all safety population analyses.
    End point type
    Secondary
    End point timeframe
    Baseline and up to Day 43
    Notes
    [152] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period.
    End point values
    		 Placebo Dapro 10 mg Dapro 15 mg Dapro 30 mg Dapro 25 mg
    Number of subjects analysed
    19 [153]
    20 [154]
    20 [155]
    22 [156]
    22 [157]
    Units: g/L
    arithmetic mean (standard deviation)
        Day 15; n= 17, 19, 17, 21, 21
    2.6 ( 11.09 )
    3.0 ( 14.21 )
    3.5 ( 10.87 )
    -5.0 ( 12.92 )
    -3.2 ( 11.48 )
        Day 29; n= 16, 19, 17, 17, 18
    5.6 ( 12.81 )
    7.3 ( 16.92 )
    7.6 ( 8.27 )
    -4.4 ( 12.30 )
    0.8 ( 10.04 )
        Day 43; n= 16, 20, 19, 20, 21
    3.9 ( 15.92 )
    3.0 ( 16.53 )
    6.0 ( 11.44 )
    -0.3 ( 9.14 )
    -1.0 ( 12.12 )
    Notes
    [153] - Safety Population
    [154] - Safety Population
    [155] - Safety Population
    [156] - Safety Population
    [157] - Safety Population
    No statistical analyses for this end point

    Secondary: Change from Baseline in MCV levels

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    End point title
    		 Change from Baseline in MCV levels [158]
    End point description
    Blood samples were collected from participants to evaluate clinical hematology parameters including MCV. Change from Baseline in clinical hematology parameters at Day 15, Day 29, Day 43 are presented. Day 1 values were considered as Baseline values. Change from Baseline was calculated by subtracting post-Baseline visit values minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). One participant was randomized to the placebo but erroneously received daprodustat 25mg and was included in the 25mg subset analysis group for all safety population analyses.
    End point type
    Secondary
    End point timeframe
    Baseline and up to Day 43
    Notes
    [158] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period.
    End point values
    		 Placebo Dapro 10 mg Dapro 15 mg Dapro 30 mg Dapro 25 mg
    Number of subjects analysed
    19 [159]
    20 [160]
    20 [161]
    22 [162]
    22 [163]
    Units: fL
    arithmetic mean (standard deviation)
        Day 15; n= 17, 19, 17, 21, 21
    -0.4 ( 2.98 )
    -0.2 ( 3.39 )
    -0.3 ( 2.57 )
    2.2 ( 3.21 )
    1.3 ( 3.15 )
        Day 29; n= 16, 19, 17, 17, 18
    -1.4 ( 3.24 )
    -0.5 ( 2.86 )
    -0.9 ( 2.36 )
    1.6 ( 2.40 )
    0.9 ( 2.54 )
        Day 43; n= 16, 20, 19, 20, 21
    -0.8 ( 3.15 )
    -0.7 ( 3.37 )
    -0.8 ( 3.28 )
    0.9 ( 2.10 )
    0.6 ( 3.06 )
    Notes
    [159] - Safety Population
    [160] - Safety Population
    [161] - Safety Population
    [162] - Safety Population
    [163] - Safety Population
    No statistical analyses for this end point

    Secondary: Change from Baseline in erythrocyte distribution width levels

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    End point title
    		 Change from Baseline in erythrocyte distribution width levels [164]
    End point description
    Blood samples were collected from participants to evaluate clinical hematology parameters including erythrocyte distribution width. Change from Baseline in clinical hematology parameters at Day 15, Day 29, Day 43 are presented. Day 1 values were considered as Baseline values. Change from Baseline was calculated by subtracting post-Baseline visit values minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). One participant was randomized to the placebo but erroneously received daprodustat 25mg and was included in the 25mg subset analysis group for all safety population analyses.
    End point type
    Secondary
    End point timeframe
    Baseline and up to Day 43
    Notes
    [164] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period.
    End point values
    		 Placebo Dapro 10 mg Dapro 15 mg Dapro 30 mg Dapro 25 mg
    Number of subjects analysed
    19 [165]
    20 [166]
    20 [167]
    22 [168]
    22 [169]
    Units: Percentage of width
    arithmetic mean (standard deviation)
        Day 15; n= 17, 19, 17, 21, 21
    -0.18 ( 1.025 )
    -0.48 ( 1.276 )
    -0.09 ( 1.047 )
    1.06 ( 1.337 )
    0.54 ( 1.162 )
        Day 29; n= 16, 19, 17, 17, 18
    -0.31 ( 1.019 )
    -0.64 ( 1.332 )
    -0.23 ( 1.021 )
    0.40 ( 1.342 )
    0.58 ( 1.202 )
        Day 43; n= 16, 20, 19, 20, 21
    0.18 ( 1.329 )
    -0.74 ( 1.728 )
    -0.50 ( 1.094 )
    -0.22 ( 1.165 )
    0.23 ( 1.410 )
    Notes
    [165] - Safety Population
    [166] - Safety Population
    [167] - Safety Population
    [168] - Safety Population
    [169] - Safety Population
    No statistical analyses for this end point

    Secondary: Change from Baseline in leukocytes, neutrophils, basophils, eosinophils, lymphocytes, monocytes, platelets levels

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    End point title
    		 Change from Baseline in leukocytes, neutrophils, basophils, eosinophils, lymphocytes, monocytes, platelets levels [170]
    End point description
    Blood samples were collected from participants to evaluate clinical hematology parameters including leukocytes, neutrophils, basophils, eosinophils, lymphocytes, monocytes, platelets. Change from Baseline in clinical hematology parameters at Day 15, Day 29, Day 43 are presented. Day 1 values were considered as Baseline values. Change from Baseline was calculated by subtracting post-Baseline visit values minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). One participant was randomized to the placebo but erroneously received daprodustat 25mg and was included in the 25mg subset analysis group for all safety population analyses.
    End point type
    Secondary
    End point timeframe
    Baseline and up to Day 43
    Notes
    [170] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period.
    End point values
    		 Placebo Dapro 10 mg Dapro 15 mg Dapro 30 mg Dapro 25 mg
    Number of subjects analysed
    19 [171]
    20 [172]
    20 [173]
    22 [174]
    22 [175]
    Units: 10^12 cells/L
    arithmetic mean (standard deviation)
        Leukocytes; Day 15; n= 17, 19, 17, 21, 21
    0.47 ( 1.271 )
    -0.21 ( 1.051 )
    0.40 ( 1.116 )
    -0.03 ( 1.463 )
    -0.03 ( 1.476 )
        Leukocytes; Day 29; n= 16, 19, 17, 17, 18
    0.49 ( 1.849 )
    0.40 ( 1.784 )
    0.00 ( 1.084 )
    0.20 ( 1.526 )
    -0.14 ( 1.701 )
        Leukocytes; Day 43; n= 16, 20, 19, 19, 20
    0.54 ( 1.041 )
    1.08 ( 1.662 )
    0.23 ( 1.101 )
    0.67 ( 1.580 )
    0.21 ( 2.615 )
        Neutrophils; Day 15; n= 17, 19, 17, 21, 21
    0.391 ( 1.2323 )
    -0.146 ( 0.9163 )
    0.280 ( 1.0681 )
    0.344 ( 1.2469 )
    0.259 ( 1.3874 )
        Neutrophils; Day 29; n= 16, 18, 17, 15, 17
    0.237 ( 1.6283 )
    0.469 ( 1.5717 )
    -0.021 ( 1.0157 )
    0.273 ( 1.5729 )
    -0.009 ( 1.8718 )
        Neutrophils; Day 43; n= 16, 20, 19, 19, 19
    0.423 ( 1.0535 )
    0.904 ( 1.3737 )
    0.112 ( 1.0449 )
    0.691 ( 1.5221 )
    0.504 ( 2.3110 )
        Basophils; Day 15; n= 17, 19, 17, 21, 21
    0.005 ( 0.0302 )
    0.009 ( 0.0200 )
    -0.002 ( 0.0210 )
    0.007 ( 0.0102 )
    -0.002 ( 0.0383 )
        Basophils; Day 29; n= 16, 18, 17, 15, 17
    0.013 ( 0.0510 )
    0.006 ( 0.0195 )
    -0.004 ( 0.0187 )
    0.012 ( 0.0328 )
    0.000 ( 0.0242 )
        Basophils; Day 43; n= 16, 20, 19, 19, 19
    0.006 ( 0.0268 )
    0.001 ( 0.0148 )
    -0.004 ( 0.0203 )
    0.007 ( 0.0192 )
    -0.001 ( 0.0228 )
        Eosinophils; Day 15; n= 17, 19, 17, 21, 21
    0.009 ( 0.0698 )
    -0.017 ( 0.1313 )
    -0.006 ( 0.1345 )
    -0.053 ( 0.1478 )
    -0.006 ( 0.1183 )
        Eosinophils; Day 29; n= 16, 18, 17, 15, 17
    0.020 ( 0.0859 )
    -0.002 ( 0.1226 )
    -0.006 ( 0.1129 )
    0.007 ( 0.0880 )
    0.025 ( 0.0990 )
        Eosinophils; Day 43; n= 16, 20, 19, 19, 19
    0.061 ( 0.1193 )
    0.030 ( 0.1439 )
    0.051 ( 0.1647 )
    -0.024 ( 0.1876 )
    0.021 ( 0.0984 )
        Lymphocytes; Day 15; n= 17, 19, 17, 21, 21
    0.082 ( 0.4256 )
    -0.019 ( 0.3163 )
    0.106 ( 0.4617 )
    -0.236 ( 0.4298 )
    -0.208 ( 0.5095 )
        Lymphocytes; Day 29; n= 16, 18, 17, 15, 17
    0.194 ( 0.6605 )
    0.026 ( 0.4130 )
    0.019 ( 0.4421 )
    -0.154 ( 0.3058 )
    -0.074 ( 0.7018 )
        Lymphocytes; Day 43; n= 16, 20, 19, 19, 19
    0.018 ( 0.3427 )
    0.061 ( 0.3332 )
    0.007 ( 0.4824 )
    -0.041 ( 0.2801 )
    -0.064 ( 0.4759 )
        Monocytes; Day 15; n= 17, 19, 17, 21, 21
    -0.005 ( 0.1518 )
    -0.042 ( 0.1504 )
    -0.016 ( 0.2285 )
    -0.037 ( 0.1460 )
    -0.068 ( 0.1895 )
        Monocytes; Day 29; n= 16, 18, 17, 15, 17
    0.027 ( 0.1553 )
    0.053 ( 0.1483 )
    -0.031 ( 0.2194 )
    0.015 ( 0.1878 )
    0.077 ( 0.2532 )
        Monocytes; Day 43; n= 16, 20, 19, 19, 19
    0.033 ( 0.1631 )
    0.065 ( 0.1629 )
    0.026 ( 0.2652 )
    0.023 ( 0.1249 )
    -0.021 ( 0.1855 )
        Platelet; Day 15; n= 17, 18, 17, 21, 20
    -14.2 ( 26.24 )
    -16.2 ( 27.46 )
    -3.2 ( 38.13 )
    -10.8 ( 31.95 )
    -3.3 ( 27.78 )
        Platelet; Day 29; n= 16, 18, 17, 17, 17
    -17.1 ( 40.58 )
    -12.8 ( 36.55 )
    -18.1 ( 29.63 )
    -2.4 ( 33.65 )
    1.3 ( 35.58 )
        Platelet; Day 43; n= 15, 19, 19, 20, 21
    -4.9 ( 37.30 )
    4.4 ( 50.34 )
    -10.4 ( 35.12 )
    -7.1 ( 31.95 )
    -1.6 ( 30.95 )
    Notes
    [171] - Safety Population
    [172] - Safety Population
    [173] - Safety Population
    [174] - Safety Population
    [175] - Safety Population
    No statistical analyses for this end point

    Secondary: Number of participants with abnormal Electrocardiogram (ECG) findings at indicated time points

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    End point title
    		 Number of participants with abnormal Electrocardiogram (ECG) findings at indicated time points [176]
    End point description
    Single measurements of 12-lead ECG were obtained in supine position using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT interval. Number of participants who had abnormal non clinically significant (NCS) and abnormal clinically significant (CS) ECG findings at Baseline (Week -4) and Day 29 are presented. One participant was randomized to the placebo but erroneously received daprodustat 25mg and was included in the 25mg subset analysis group for all safety population analyses.
    End point type
    Secondary
    End point timeframe
    Up to Day 29
    Notes
    [176] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period.
    End point values
    		 Placebo Dapro 10 mg Dapro 15 mg Dapro 30 mg Dapro 25 mg
    Number of subjects analysed
    19 [177]
    20 [178]
    20 [179]
    22 [180]
    22 [181]
    Units: Participants
        Baseline(Week -4);Abnormal; NCS;n=19,20,20,22,22
    10
    15
    18
    16
    12
        Baseline(Week-4);Abnormal;CS;n=19,20,20,22,22
    0
    0
    0
    0
    1
        Day 29; Abnormal; NCS; n=17,19,18,17, 19
    12
    14
    16
    12
    8
        Day 29; Abnormal; CS; n=17,19,18,17, 19
    0
    0
    0
    0
    1
    Notes
    [177] - Safety Population
    [178] - Safety Population
    [179] - Safety Population
    [180] - Safety Population
    [181] - Safety Population
    No statistical analyses for this end point

    Secondary: Change from Baseline in ECG mean heart rate

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    End point title
    		 Change from Baseline in ECG mean heart rate
    End point description
    Single measurements of 12-lead ECG were obtained in supine position using an ECG machine to measure HR. Week -4 values were considered as Baseline values. Change from Baseline was calculated by subtracting post-Baseline visit values at Day 29 minus Baseline value.
    End point type
    Secondary
    End point timeframe
    Baseline and Day 29
    End point values
    		 Placebo Dapro 10 mg Dapro 15 mg Dapro 25 mg Dapro 30 mg
    Number of subjects analysed
    17 [182]
    19 [183]
    18 [184]
    19 [185]
    17 [186]
    Units: Beats per minute
    arithmetic mean (standard deviation)
        Beats per minute
    -2.0 ( 8.66 )
    0.5 ( 10.53 )
    1.1 ( 7.40 )
    2.2 ( 7.51 )
    0.9 ( 7.09 )
    Notes
    [182] - Safety Population
    [183] - Safety Population
    [184] - Safety Population
    [185] - Safety Population
    [186] - Safety Population
    No statistical analyses for this end point

    Secondary: Change from Baseline in ECG parameters including PR interval, QRS duration, QT interval and QTcB

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    End point title
    		 Change from Baseline in ECG parameters including PR interval, QRS duration, QT interval and QTcB [187]
    End point description
    Single measurements of 12-lead ECG were obtained in supine position using an ECG machine to measure PR interval, QRS duration, QT interval and QTcB. Week -4 values were considered as Baseline values. Change from Baseline was calculated by subtracting post-Baseline visit values at Day 29 minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). One participant was randomized to the placebo but erroneously received daprodustat 25mg and was included in the 25mg subset analysis group for all safety population analyses.
    End point type
    Secondary
    End point timeframe
    Baseline and Day 29
    Notes
    [187] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period.
    End point values
    		 Placebo Dapro 10 mg Dapro 15 mg Dapro 30 mg Dapro 25 mg
    Number of subjects analysed
    19 [188]
    20 [189]
    20 [190]
    22 [191]
    22 [192]
    Units: Milliseconds (msec)
    arithmetic mean (standard deviation)
        PR interval; n= 17, 18, 18, 16, 17
    7.8 ( 16.86 )
    7.3 ( 12.37 )
    -3.3 ( 23.04 )
    -11.5 ( 24.77 )
    2.1 ( 27.13 )
        QRS duration; n= 17, 19, 18, 17, 19
    -1.4 ( 14.05 )
    -5.7 ( 13.36 )
    -4.7 ( 47.01 )
    2.5 ( 8.97 )
    1.7 ( 14.33 )
        QT interval; n= 17, 19, 18, 17, 19
    10.5 ( 27.16 )
    0.7 ( 31.11 )
    -19.2 ( 62.37 )
    -8.2 ( 33.24 )
    -1.4 ( 17.72 )
        QTcB; n= 17, 19, 18, 17, 19
    0.0 ( 30.84 )
    5.6 ( 17.40 )
    -3.7 ( 44.86 )
    -5.7 ( 31.65 )
    1.1 ( 20.84 )
    Notes
    [188] - Safety Population
    [189] - Safety Population
    [190] - Safety Population
    [191] - Safety Population
    [192] - Safety Population
    No statistical analyses for this end point

    Secondary: Systolic blood pressure (SBP) and diastolic blood pressure (DBP) values at pre-dialysis and post-dialysis

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    End point title
    		 Systolic blood pressure (SBP) and diastolic blood pressure (DBP) values at pre-dialysis and post-dialysis [193]
    End point description
    Vital sign measurements including SBP and DBP were taken in a seated or semi-supine position in the dialysis chair at specific time points. SBP and DBP were measured pre-dialysis and post-dialysis. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). One participant was randomized to the placebo but erroneously received daprodustat 25mg and was included in the 25mg subset analysis group for all safety population analyses.
    End point type
    Secondary
    End point timeframe
    Up to Day 43
    Notes
    [193] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period.
    End point values
    		 Placebo Dapro 10 mg Dapro 15 mg Dapro 30 mg Dapro 25 mg
    Number of subjects analysed
    19 [194]
    20 [195]
    20 [196]
    22 [197]
    22 [198]
    Units: Millimeter of mercury (mmHg)
    arithmetic mean (standard deviation)
        SBP; pre-dialysis; Day 1; n= 19, 20, 20, 22, 22
    142.5 ( 22.15 )
    136.6 ( 15.39 )
    149.2 ( 26.36 )
    144.1 ( 17.01 )
    144.1 ( 24.27 )
        SBP; pre-dialysis; Day 15; n= 17, 20, 18, 21, 22
    138.8 ( 24.12 )
    138.3 ( 16.14 )
    139.0 ( 22.77 )
    142.3 ( 14.90 )
    146.6 ( 20.75 )
        SBP; pre-dialysis; Day 29; n= 17, 19, 18, 17, 19
    143.0 ( 22.08 )
    133.1 ( 18.65 )
    143.1 ( 23.21 )
    148.7 ( 19.17 )
    144.2 ( 23.27 )
        SBP; pre-dialysis; Day 43; n= 16, 20, 19, 21, 21
    140.0 ( 22.01 )
    137.9 ( 13.21 )
    142.0 ( 24.23 )
    147.1 ( 19.18 )
    149.0 ( 23.32 )
        DBP; pre-dialysis; Day 1; n= 19, 20, 20, 22, 22
    71.9 ( 14.84 )
    68.8 ( 11.02 )
    73.3 ( 12.96 )
    72.2 ( 13.64 )
    71.8 ( 14.38 )
        DBP; pre-dialysis; Day 15; n= 17, 20, 18, 21, 22
    72.5 ( 17.76 )
    70.0 ( 11.92 )
    70.1 ( 10.50 )
    69.7 ( 12.43 )
    73.5 ( 13.69 )
        DBP; pre-dialysis; Day 29; n= 17, 19, 18, 17, 19
    70.4 ( 15.43 )
    63.5 ( 13.55 )
    70.9 ( 12.86 )
    72.7 ( 9.96 )
    73.3 ( 13.17 )
        DBP; pre-dialysis; Day 43; n= 16, 20, 19, 21, 21
    72.5 ( 14.73 )
    66.8 ( 11.94 )
    69.9 ( 13.54 )
    72.8 ( 10.52 )
    77.9 ( 16.03 )
        SBP; post-dialysis; Day 1; n= 19, 20, 20, 22, 22
    138.6 ( 18.57 )
    137.0 ( 22.10 )
    139.9 ( 22.24 )
    140.1 ( 20.10 )
    136.7 ( 21.15 )
        SBP; post-dialysis; Day 15; n= 17, 20, 18, 21, 22
    138.6 ( 21.83 )
    135.5 ( 21.63 )
    137.7 ( 23.02 )
    140.9 ( 15.34 )
    137.4 ( 17.58 )
        SBP; post-dialysis; Day 29; n= 17, 19, 18, 17, 19
    135.7 ( 26.04 )
    130.1 ( 18.50 )
    133.7 ( 23.88 )
    147.8 ( 19.09 )
    142.8 ( 23.96 )
        SBP; post-dialysis; Day 43; n= 16, 20, 19, 21, 21
    137.5 ( 22.74 )
    135.8 ( 21.05 )
    130.4 ( 15.47 )
    137.5 ( 22.74 )
    145.2 ( 20.66 )
        DBP; post-dialysis; Day 1; n= 19, 20, 20, 22, 22
    72.1 ( 15.11 )
    67.9 ( 11.49 )
    68.7 ( 11.64 )
    71.5 ( 11.17 )
    71.1 ( 12.92 )
        DBP; post-dialysis; Day 15; n= 17, 20, 18, 21, 22
    72.4 ( 16.41 )
    70.1 ( 12.84 )
    67.8 ( 11.10 )
    71.1 ( 9.51 )
    71.3 ( 11.07 )
        DBP; post-dialysis; Day 29; n= 17, 19, 18, 17, 19
    73.9 ( 15.11 )
    64.4 ( 9.83 )
    67.9 ( 12.00 )
    72.9 ( 11.18 )
    72.4 ( 12.43 )
        DBP; post-dialysis; Day 43; n= 16, 20, 19, 21, 21
    69.5 ( 15.24 )
    67.4 ( 10.90 )
    67.4 ( 11.24 )
    75.3 ( 7.89 )
    72.9 ( 12.60 )
    Notes
    [194] - Safety Population
    [195] - Safety Population
    [196] - Safety Population
    [197] - Safety Population
    [198] - Safety Population
    No statistical analyses for this end point

    Secondary: Pulse rate values at pre-dialysis and post-dialysis

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    End point title
    		 Pulse rate values at pre-dialysis and post-dialysis [199]
    End point description
    Vital sign measurements including pulse rate values were taken in a seated or semi-supine position in the dialysis chair. Pulse rate was measured pre-dialysis and post-dialysis. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). One participant was randomized to the placebo but erroneously received daprodustat 25mg and was included in the 25mg subset analysis group for all safety population analyses.
    End point type
    Secondary
    End point timeframe
    Up to Day 43
    Notes
    [199] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period.
    End point values
    		 Placebo Dapro 10 mg Dapro 15 mg Dapro 30 mg Dapro 25 mg
    Number of subjects analysed
    19 [200]
    20 [201]
    20 [202]
    22 [203]
    22 [204]
    Units: Beats per minute
    arithmetic mean (standard deviation)
        Pre-dialysis; Day 1; n= 19, 20, 20, 22, 22
    68.5 ( 7.95 )
    69.9 ( 9.18 )
    66.7 ( 7.01 )
    76.5 ( 9.35 )
    71.4 ( 11.25 )
        Pre-dialysis; Day 15; n= 17, 20, 18, 21, 22
    76.1 ( 10.31 )
    67.3 ( 9.20 )
    68.3 ( 7.51 )
    75.1 ( 12.68 )
    72.1 ( 11.89 )
        Pre-dialysis; Day 29; n= 17, 19, 18, 17, 19
    70.4 ( 8.31 )
    70.3 ( 11.54 )
    69.6 ( 9.53 )
    73.4 ( 11.45 )
    70.8 ( 9.91 )
        Pre-dialysis; Day 43; n= 16, 20, 19, 21, 21
    71.5 ( 9.17 )
    69.9 ( 9.34 )
    66.9 ( 6.74 )
    75.8 ( 8.29 )
    71.3 ( 10.08 )
        Post-dialysis; Day 1; n= 19, 20, 20, 22, 22
    71.0 ( 11.54 )
    68.7 ( 11.19 )
    66.3 ( 8.37 )
    78.8 ( 11.61 )
    73.2 ( 12.77 )
        Post-dialysis; Day 15; n= 17, 20, 18, 21, 22
    72.5 ( 12.69 )
    67.7 ( 12.24 )
    70.1 ( 12.49 )
    78.1 ( 15.72 )
    73.0 ( 12.07 )
        Post-dialysis; Day 29; n= 17, 19, 18, 17, 19
    73.6 ( 7.10 )
    69.9 ( 9.60 )
    68.8 ( 11.29 )
    77.4 ( 10.04 )
    72.2 ( 9.52 )
        Post-dialysis; Day 43; n= 16, 20, 19, 21, 21
    72.0 ( 12.04 )
    69.1 ( 10.21 )
    68.0 ( 10.28 )
    77.3 ( 10.26 )
    71.9 ( 11.02 )
    Notes
    [200] - Safety Population
    [201] - Safety Population
    [202] - Safety Population
    [203] - Safety Population
    [204] - Safety Population
    No statistical analyses for this end point

    Secondary: Weight values at post-dialysis

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    End point title
    		 Weight values at post-dialysis [205]
    End point description
    Vital sign measurements including weight values were taken in a seated or semi-supine position in the dialysis chair. Weight was measured post-dialysis. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). One participant was randomized to the placebo but erroneously received daprodustat 25mg and was included in the 25mg subset analysis group for all safety population analyses.
    End point type
    Secondary
    End point timeframe
    Up to Day 43
    Notes
    [205] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period.
    End point values
    		 Placebo Dapro 10 mg Dapro 15 mg Dapro 30 mg Dapro 25 mg
    Number of subjects analysed
    19 [206]
    20 [207]
    20 [208]
    22 [209]
    22 [210]
    Units: Kilograms (kg)
    arithmetic mean (standard deviation)
        Day 1; n= 19, 20, 20, 22, 22
    82.38 ( 25.941 )
    80.04 ( 25.996 )
    78.83 ( 21.331 )
    76.03 ( 16.877 )
    79.38 ( 23.345 )
        Day 15; n= 17, 20, 18, 21, 22
    84.24 ( 26.652 )
    80.00 ( 25.887 )
    79.82 ( 22.200 )
    75.55 ( 17.595 )
    79.44 ( 23.500 )
        Day 29; n= 17, 19, 18, 17, 19
    83.22 ( 27.198 )
    81.04 ( 25.925 )
    80.02 ( 22.286 )
    76.07 ( 18.135 )
    82.66 ( 23.036 )
        Day 43; n= 16, 20, 19, 21, 21
    83.93 ( 27.589 )
    80.21 ( 26.683 )
    79.25 ( 21.757 )
    73.66 ( 11.614 )
    80.64 ( 23.347 )
    Notes
    [206] - Safety Population
    [207] - Safety Population
    [208] - Safety Population
    [209] - Safety Population
    [210] - Safety Population
    No statistical analyses for this end point

    Secondary: Change from Baseline in SBP and DBP values at pre-dialysis and post-dialysis

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    End point title
    		 Change from Baseline in SBP and DBP values at pre-dialysis and post-dialysis [211]
    End point description
    Vital sign measurements including SBP and DBP were taken in a seated or semi-supine position in the dialysis chair. SBP and DBP were measured pre-dialysis and post-dialysis. Pre-dialysis Baseline value was defined as SBP and DBP value obtained pre-dialysis on Day 1. Post-dialysis Baseline value was defined as SBP and DBP value obtained post-dialysis at Week -2. Change from Baseline was calculated by subtracting post-Baseline visit values minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). One participant was randomized to the placebo but erroneously received daprodustat 25mg and was included in the 25mg subset analysis group for all safety population analyses.
    End point type
    Secondary
    End point timeframe
    Up to Day 43
    Notes
    [211] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period.
    End point values
    		 Placebo Dapro 10 mg Dapro 15 mg Dapro 30 mg Dapro 25 mg
    Number of subjects analysed
    19 [212]
    20 [213]
    20 [214]
    22 [215]
    22 [216]
    Units: mmHg
    arithmetic mean (standard deviation)
        SBP; pre-dialysis; Day 15; n= 17, 20, 18, 21, 22
    -2.9 ( 22.03 )
    1.7 ( 14.14 )
    -5.6 ( 14.77 )
    -1.4 ( 16.35 )
    2.5 ( 20.68 )
        SBP; pre-dialysis; Day 29; n= 17, 19, 18, 17, 19
    -0.6 ( 20.32 )
    -3.9 ( 19.72 )
    -4.7 ( 18.17 )
    4.5 ( 20.03 )
    1.3 ( 17.51 )
        SBP; pre-dialysis; Day 43; n= 16, 20, 19, 21, 21
    -2.1 ( 21.34 )
    1.2 ( 17.14 )
    -6.2 ( 13.83 )
    4.3 ( 10.03 )
    3.3 ( 19.47 )
        SBP; post-dialysis; Day 15; n= 17, 20, 18, 21, 22
    5.4 ( 21.39 )
    -3.6 ( 20.13 )
    6.1 ( 20.81 )
    -0.7 ( 22.33 )
    5.7 ( 21.07 )
        SBP; post-dialysis; Day 29; n= 17, 19, 18, 17, 19
    2.3 ( 19.72 )
    -9.4 ( 18.50 )
    0.8 ( 24.79 )
    4.0 ( 19.76 )
    9.3 ( 19.03 )
        SBP; post-dialysis; Day 43; n= 16, 20, 19, 21, 21
    3.1 ( 22.22 )
    -3.2 ( 21.71 )
    -3.6 ( 17.88 )
    4.7 ( 20.11 )
    12.0 ( 20.19 )
        DBP; pre-dialysis; Day 15; n= 17, 20, 18, 21, 22
    1.1 ( 10.57 )
    1.2 ( 8.85 )
    -1.7 ( 9.78 )
    -2.1 ( 11.04 )
    1.8 ( 12.68 )
        DBP; pre-dialysis; Day 29; n= 17, 19, 18, 17, 19
    -0.3 ( 11.09 )
    -4.7 ( 10.04 )
    -3.0 ( 8.99 )
    -0.1 ( 13.80 )
    1.4 ( 10.50 )
        DBP; pre-dialysis; Day 43; n= 16, 20, 19, 21, 21
    2.2 ( 8.80 )
    -2.0 ( 9.47 )
    -3.1 ( 11.06 )
    2.1 ( 11.00 )
    5.2 ( 15.08 )
        DBP; post-dialysis; Day 15; n= 17, 20, 18, 21, 22
    2.4 ( 11.41 )
    2.4 ( 7.71 )
    -2.9 ( 11.11 )
    -0.8 ( 14.13 )
    3.6 ( 9.84 )
        DBP; post-dialysis; Day 29; n= 17, 19, 18, 17, 19
    3.7 ( 12.93 )
    -2.5 ( 8.52 )
    -3.2 ( 11.61 )
    0.2 ( 10.59 )
    4.1 ( 9.33 )
        DBP; post-dialysis; Day 43; n= 16, 20, 19, 21, 21
    -0.6 ( 10.07 )
    -0.3 ( 9.53 )
    -3.8 ( 12.13 )
    4.8 ( 10.28 )
    4.5 ( 9.99 )
    Notes
    [212] - Safety Population
    [213] - Safety Population
    [214] - Safety Population
    [215] - Safety Population
    [216] - Safety Population
    No statistical analyses for this end point

    Secondary: Change from Baseline in pulse rate value at pre-dialysis and post-dialysis

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    End point title
    		 Change from Baseline in pulse rate value at pre-dialysis and post-dialysis [217]
    End point description
    Vital sign measurements including pulse rate were taken in a seated or semi-supine position in the dialysis chair. Pulse rate was measured pre-dialysis and post-dialysis. Pre-dialysis Baseline value was defined as pulse rate value obtained pre-dialysis on Day 1. Post-dialysis Baseline value was defined as pulse rate value obtained post-dialysis at Week -2. Change from Baseline was calculated by subtracting post-Baseline visit values minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). One participant was randomized to the placebo but erroneously received daprodustat 25mg and was included in the 25mg subset analysis group for all safety population analyses.
    End point type
    Secondary
    End point timeframe
    Up to Day 43
    Notes
    [217] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period.
    End point values
    		 Placebo Dapro 10 mg Dapro 15 mg Dapro 30 mg Dapro 25 mg
    Number of subjects analysed
    19 [218]
    20 [219]
    20 [220]
    22 [221]
    22 [222]
    Units: Beats per minute
    arithmetic mean (standard deviation)
        Pre-dialysis; Day 15; n= 17, 20, 18, 21, 22
    7.0 ( 9.50 )
    -2.6 ( 8.46 )
    2.3 ( 5.76 )
    -1.4 ( 11.15 )
    0.7 ( 11.46 )
        Pre-dialysis; Day 29; n= 17, 19, 18, 17, 19
    2.4 ( 6.92 )
    0.9 ( 12.86 )
    3.4 ( 7.58 )
    -3.0 ( 9.14 )
    0.5 ( 10.01 )
        Pre-dialysis; Day 43; n= 16, 20, 19, 21, 21
    3.1 ( 9.59 )
    0.1 ( 6.57 )
    0.8 ( 6.11 )
    0.2 ( 6.79 )
    -0.6 ( 10.03 )
        Post-dialysis; Day 15; n= 17, 20, 18, 21, 22
    2.2 ( 11.61 )
    -1.2 ( 12.86 )
    1.1 ( 10.15 )
    4.4 ( 13.28 )
    0.5 ( 8.00 )
        Post-dialysis; Day 29; n= 17, 19, 18, 17, 19
    4.2 ( 9.13 )
    1.5 ( 13.13 )
    -0.8 ( 9.79 )
    6.0 ( 7.50 )
    2.6 ( 9.04 )
        Post-dialysis; Day 43; n= 16, 20, 19, 21, 21
    2.3 ( 8.67 )
    0.3 ( 12.96 )
    -0.8 ( 9.32 )
    3.9 ( 9.32 )
    -0.1 ( 9.08 )
    Notes
    [218] - Safety Population
    [219] - Safety Population
    [220] - Safety Population
    [221] - Safety Population
    [222] - Safety Population
    No statistical analyses for this end point

    Secondary: Change from Baseline in weight at post-dialysis

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    End point title
    		 Change from Baseline in weight at post-dialysis [223]
    End point description
    Vital sign measurements including weight were taken in a seated or semi-supine position in the dialysis chair. Weight was measured post-dialysis. Post-dialysis Baseline value was defined as SBP and DBP value obtained post-dialysis at Week -2. Change from Baseline was calculated by subtracting post-Baseline visit values minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). One participant was randomized to the placebo but erroneously received daprodustat 25mg and was included in the 25mg subset analysis group for all safety population analyses.
    End point type
    Secondary
    End point timeframe
    Up to Day 43
    Notes
    [223] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period.
    End point values
    		 Placebo Dapro 10 mg Dapro 15 mg Dapro 30 mg Dapro 25 mg
    Number of subjects analysed
    19 [224]
    20 [225]
    20 [226]
    22 [227]
    22 [228]
    Units: kg
    arithmetic mean (standard deviation)
        Day 15; n= 17, 20, 18, 21, 22
    -0.16 ( 0.634 )
    0.16 ( 0.971 )
    -0.01 ( 0.617 )
    -0.31 ( 1.215 )
    0.06 ( 0.799 )
        Day 29; n= 17, 19, 18, 17, 19
    -0.11 ( 1.053 )
    -0.05 ( 1.583 )
    -1.23 ( 5.913 )
    -0.19 ( 1.244 )
    -0.16 ( 1.046 )
        Day 43; n= 16, 20, 19, 21, 21
    -0.21 ( 0.665 )
    0.37 ( 2.760 )
    -1.39 ( 5.759 )
    0.33 ( 2.169 )
    0.15 ( 1.472 )
    Notes
    [224] - Safety Population
    [225] - Safety Population
    [226] - Safety Population
    [227] - Safety Population
    [228] - Safety Population
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    On-therapy serious adverse events (SAEs) and non-serious adverse events (AEs) are presented from the start of study treatment to the end of the 29-day study treatment period plus 1 day, inclusive; an average of 30 days.
    Adverse event reporting additional description
    On-therapy SAEs and non-serious AEs are reported for the safety Population, comprised of all participants who received at least one dose of investigational drug. One participant who was randomized to the placebo group, erroneously received 25mg daprodustat treatment throughout treatment period and was counted within the Daprodustat 25mg group.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    19.1
    Reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Randomized participants received placebo tablet via oral route three times weekly for 29 days.

    Reporting group title
    Dapro 10 mg
    Reporting group description
    		 Randomized participants received dapro 10 mg tablet via oral route three times weekly for 29 days.

    Reporting group title
    Dapro 15 mg
    Reporting group description
    		 Randomized participants received dapro 15 mg tablet via oral route three times weekly for 29 days.

    Reporting group title
    Dapro 25 mg
    Reporting group description
    		 Randomized participants received dapro 25 mg tablet via oral route three times weekly for 29 days.

    Reporting group title
    Dapro 30 mg
    Reporting group description
    		 Randomized participants received dapro 30 mg tablet via oral route three times weekly for 29 days

    Serious adverse events
    		 Placebo Dapro 10 mg Dapro 15 mg Dapro 25 mg Dapro 30 mg
    Total subjects affected by serious adverse events
         subjects affected / exposed
    2 / 19 (10.53%)
    3 / 20 (15.00%)
    2 / 20 (10.00%)
    1 / 22 (4.55%)
    2 / 22 (9.09%)
         number of deaths (all causes)
    0
    0
    0
    0
    0
         number of deaths resulting from adverse events
    Injury, poisoning and procedural complications
    Arteriovenous fistula thrombosis
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 22 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Post procedural myocardial infarction
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 20 (5.00%)
    0 / 20 (0.00%)
    0 / 22 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Hypertensive crisis
         subjects affected / exposed
    0 / 19 (0.00%)
    0 / 20 (0.00%)
    1 / 20 (5.00%)
    0 / 22 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Orthostatic hypotension
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 22 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Angina unstable
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 20 (5.00%)
    0 / 20 (0.00%)
    0 / 22 (0.00%)
    1 / 22 (4.55%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac failure congestive
         subjects affected / exposed
    0 / 19 (0.00%)
    2 / 20 (10.00%)
    0 / 20 (0.00%)
    0 / 22 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Mesenteric artery stenosis
         subjects affected / exposed
    0 / 19 (0.00%)
    0 / 20 (0.00%)
    1 / 20 (5.00%)
    0 / 22 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Fluid overload
         subjects affected / exposed
    0 / 19 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    1 / 22 (4.55%)
    1 / 22 (4.55%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Placebo Dapro 10 mg Dapro 15 mg Dapro 25 mg Dapro 30 mg
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    5 / 19 (26.32%)
    8 / 20 (40.00%)
    4 / 20 (20.00%)
    2 / 22 (9.09%)
    0 / 22 (0.00%)
    Injury, poisoning and procedural complications
    Arteriovenous fistula site haemorrhage
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 20 (5.00%)
    0 / 20 (0.00%)
    0 / 22 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Procedural hypotension
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 20 (5.00%)
    0 / 20 (0.00%)
    1 / 22 (4.55%)
    0 / 22 (0.00%)
         occurrences all number
    0
    1
    0
    1
    0
    Vascular disorders
    Hypotension
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 20 (5.00%)
    1 / 20 (5.00%)
    1 / 22 (4.55%)
    0 / 22 (0.00%)
         occurrences all number
    0
    1
    1
    1
    0
    Cardiac disorders
    Bundle branch block left
         subjects affected / exposed
    0 / 19 (0.00%)
    0 / 20 (0.00%)
    1 / 20 (5.00%)
    0 / 22 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    1 / 19 (5.26%)
    1 / 20 (5.00%)
    0 / 20 (0.00%)
    0 / 22 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    1
    1
    0
    0
    0
    Headache
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 22 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 20 (0.00%)
    1 / 20 (5.00%)
    0 / 22 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    Pyrexia
         subjects affected / exposed
    0 / 19 (0.00%)
    0 / 20 (0.00%)
    1 / 20 (5.00%)
    0 / 22 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    0 / 19 (0.00%)
    2 / 20 (10.00%)
    0 / 20 (0.00%)
    0 / 22 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    2
    0
    0
    0
    Dyspepsia
         subjects affected / exposed
    0 / 19 (0.00%)
    0 / 20 (0.00%)
    1 / 20 (5.00%)
    0 / 22 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Gastrooesophageal reflux disease
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 20 (5.00%)
    0 / 20 (0.00%)
    0 / 22 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Vomiting
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 20 (5.00%)
    0 / 20 (0.00%)
    0 / 22 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Respiratory, thoracic and mediastinal disorders
    Catarrh
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 20 (5.00%)
    0 / 20 (0.00%)
    0 / 22 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Psychiatric disorders
    Depression
         subjects affected / exposed
    0 / 19 (0.00%)
    0 / 20 (0.00%)
    1 / 20 (5.00%)
    0 / 22 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Endocrine disorders
    Hyperparathyroidism
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 20 (5.00%)
    0 / 20 (0.00%)
    0 / 22 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Musculoskeletal and connective tissue disorders
    Muscle spasms
         subjects affected / exposed
    0 / 19 (0.00%)
    0 / 20 (0.00%)
    1 / 20 (5.00%)
    0 / 22 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Musculoskeletal pain
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 22 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Infections and infestations
    Helicobacter gastritis
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 22 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Pneumonia
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 20 (5.00%)
    0 / 20 (0.00%)
    0 / 22 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Upper respiratory tract infection
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 20 (5.00%)
    0 / 20 (0.00%)
    0 / 22 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Viral infection
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 20 (5.00%)
    0 / 20 (0.00%)
    0 / 22 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 22 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Hypoglycaemia
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 20 (5.00%)
    0 / 20 (0.00%)
    0 / 22 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    11 May 2016
    1. Inclusion criterion number 5 was modified to include the complete timeframe in which this criterion is applicable. 2. Other eligibility criteria have been clarified or updated for consistency with project level requirements. 3. Minor clarifications were made throughout the protocol, including clarifications related to hemoglobin stopping criteria, wording of the adverse events of special interest (AESIs), visit windows and the Time and Events Table. 4. References to investigational brochure (IB) Supplements 1 and 2 were added, and corresponding updates to the Risk Assessment Table were made. 5. Flexible language was added to allow for subjects to be dosed outside of the study clinic in exceptional circumstances. 6. The definition of the pharmacokinetic (PK) analysis population was added.

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
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