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    Clinical Trial Results:
    A randomized, repeat dose, open label, parallel group, multi-center study to evaluate the effect of daprodustat compared to darbepoetin alfa on forearm blood flow in participants with anemia of chronic kidney disease that are not dialysis dependent

    Summary
    EudraCT number
    		 2017-002268-42
    Trial protocol
    		 GB  
    Global end of trial date
    29 May 2019

    Results information
    Results version number
    		 v2(current)
    This version publication date
    23 Jul 2021
    First version publication date
    03 Jun 2021
    Other versions
    		 v1
    Version creation reason

    Trial information

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    Trial identification
    Sponsor protocol code
    205767
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03446612
    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 8664357343, GSKClinicalSupportHD@gsk.com
    Scientific contact
    GSK Response Center, GlaxoSmithKline, 1 8664357343, GSKClinicalSupportHD@gsk.com
    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
    17 Dec 2020
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    29 May 2019
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    To compare the effect of daprodustat to darbepoetin alfa on endothelial function in participants with anemia of chronic kidney disease that are not dialysis dependent
    Protection of trial subjects
    Not applicable
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    10 Jan 2019
    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 Kingdom: 6
    Worldwide total number of subjects
    6
    EEA total number of subjects
    0
    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)
    5
    From 65 to 84 years
    1
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 This was an open label, parallel group study that evaluated the effect of daprodustat and darbepoetin alfa on forearm blood flow (FBF) in participants with anemia of chronic kidney disease that are not dialysis dependent.

    Pre-assignment
    Screening details
    		 Participants were enrolled in multiple centers in United Kingdom. A total of 6 participants were enrolled in the study and only 5 participants were randomized to receive study treatment.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Daprodustat
    Arm description
    		 Participants were randomized to receive 2 milligram (mg) daprodustat tablets once daily via oral route for a period of 41 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 was available as 1 milligrams (mg), 2 mg and 4 mg oral tablets. Daprodustat was administered once daily by oral route without regard for food

    Arm title
    		 Darbepoetin alfa
    Arm description
    		 Participants were randomized to receive darbepoetin alfa solution for injection, administered as a single subcutaneous injection, once every two weeks (Days 1, 14 and 28).
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Darbepoetin alfa
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Darbepoetin alfa was given as solution for injection for subcutaneous administration every 2 weeks

    Number of subjects in period 1 [1]
    		Daprodustat Darbepoetin alfa
    Started
    2
    3
    Completed
    2
    2
    Not completed
    0
    1
         Protocol defined stopping criteria
    -
    1
    Notes
    [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
    Justification: A total of 6 participants were enrolled in the study and only 5 participants were randomized to receive study treatment.

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Daprodustat
    Reporting group description
    		 Participants were randomized to receive 2 milligram (mg) daprodustat tablets once daily via oral route for a period of 41 days.

    Reporting group title
    Darbepoetin alfa
    Reporting group description
    		 Participants were randomized to receive darbepoetin alfa solution for injection, administered as a single subcutaneous injection, once every two weeks (Days 1, 14 and 28).

    Reporting group values
    		 Daprodustat Darbepoetin alfa Total
    Number of subjects
    		 2 3 5
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    		 2 2 4
        From 65-84 years
    		 0 1 1
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    		 62.0 ( 2.83 ) 53.0 ( 15.72 ) -
    Sex: Female, Male
    Units: Participants
        Female
    		 1 1 2
        Male
    		 1 2 3
    Race/Ethnicity, Customized
    Units: Subjects
        White/Caucasian/European Heritage
    		 2 3 5

    End points

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    End points reporting groups
    Reporting group title
    Daprodustat
    Reporting group description
    		 Participants were randomized to receive 2 milligram (mg) daprodustat tablets once daily via oral route for a period of 41 days.

    Reporting group title
    Darbepoetin alfa
    Reporting group description
    		 Participants were randomized to receive darbepoetin alfa solution for injection, administered as a single subcutaneous injection, once every two weeks (Days 1, 14 and 28).

    Subject analysis set title
    Daprodustat, Darbepoetin alfa
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    This arm is a combination of Daprodustat and Darbepoetin alfa Arm to present difference in FBF ratio

    Subject analysis set title
    Daprodustat, Darbepoetin alfa
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    This arm is a combination of Daprodustat and Darbepoetin alfa Arm to present difference in FBF ratio

    Primary: Change in FBF ratio in response to acetylcholine (Day 1 to Day 42)

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    End point title
    		 Change in FBF ratio in response to acetylcholine (Day 1 to Day 42) [1]
    End point description
    Venous occlusion plethysmography was used for FBF assessment. Acetylcholine was infused intra-arterially at 7.5, 15 and 30 micrograms/minute (ug/min) each for 6 minutes per infusion. FBF ratio was defined as the ratio of a participant’s treatment (infused) arm value divided by the non-treatment (non-infused) arm value. The overall ratio was determined by taking the participant’s Day 42 FBF ratio and dividing by the Day 1 FBF ratio. Change in FBF ratio was the difference between daprodustat and darbepoetin alfa FBF ratio. Pharmacodynamic Per-Protocol (PDPP) population included all randomized participants who provided pharmacodynamic (PD) data at Day 1 and Day 42. PDPP Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles). 99999 indicates standard deviation could not be calculated as a single participant was analyzed.
    End point type
    Primary
    End point timeframe
    Day 1 to Day 42
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: There are no statistical data to report
    End point values
    		 Daprodustat, Darbepoetin alfa
    Number of subjects analysed
    2
    Units: Ratio
    arithmetic mean (standard deviation)
        7.5 ug/min, n=2
    0.6953 ( 0.12998 )
        15 ug/min, n=1
    0.1683 ( 99999 )
        30 ug/min, n=1
    0.3238 ( 99999 )
    No statistical analyses for this end point

    Secondary: Change in the absolute FBF from Day 1 to Day 42 in response to acetylcholine

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    End point title
    		 Change in the absolute FBF from Day 1 to Day 42 in response to acetylcholine
    End point description
    Venous occlusion plethysmography was used for FBF assessment. Acetylcholine was infused intra-arterially at 7.5, 15 and 30 ug/min each for 6 minutes per infusion. Measures were made in both arms concurrently. Change in the absolute FBF from Day 1 to Day 42 in response to acetylcholine is the difference between absolute value of FBF in infused arm on Day 1 and Day 42 in response to acetylcholine. PDPP Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles). 99999 indicates standard deviation could not be calculated as a single participant was analyzed.
    End point type
    Secondary
    End point timeframe
    Day 1 to Day 42
    End point values
    		 Daprodustat Darbepoetin alfa
    Number of subjects analysed
    2
    2
    Units: ug/min
    arithmetic mean (standard deviation)
        7.5 ug/min, n=2, 2
    8.3180 ( 4.50592 )
    -6.0360 ( 3.09976 )
        15 ug/min, n=1, 2
    -4.6374 ( 99999 )
    -8.8299 ( 9.98143 )
        30 ug/min, n=1, 2
    -2.6735 ( 99999 )
    -4.5121 ( 5.66731 )
    No statistical analyses for this end point

    Secondary: Change in FBF ratio in response to sodium nitroprusside (Day 1 to Day 42)

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    End point title
    		 Change in FBF ratio in response to sodium nitroprusside (Day 1 to Day 42)
    End point description
    Venous occlusion plethysmography was used for FBF assessment. Sodium nitroprusside was infused at 3 and 10 micrograms/minute each for 6 minutes per infusion into the brachial artery of the test arm. FBF ratio was defined as the ratio of a participant’s treatment (infused) arm value divided by the non-treatment (non-infused) arm value. The overall ratio was determined by taking the participant’s Day 42 FBF ratio and dividing by the Day 1 FBF ratio. Change in FBF ratio was the difference between daprodustat and darbepoetin alfa FBF ratio. PDPP Population. Only those participants with data available at the specified data points were analyzed. 99999 indicates standard deviation could not be calculated as a single participant was analyzed.
    End point type
    Secondary
    End point timeframe
    Day 1 to Day 42
    End point values
    		 Daprodustat, Darbepoetin alfa
    Number of subjects analysed
    1
    Units: Ratio
    arithmetic mean (standard deviation)
        3 ug/min
    0.2968 ( 99999 )
        10 ug/min
    1.4425 ( 99999 )
    No statistical analyses for this end point

    Secondary: Change in the absolute FBF from Day 1 to Day 42 in response to sodium nitroprusside

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    End point title
    		 Change in the absolute FBF from Day 1 to Day 42 in response to sodium nitroprusside
    End point description
    Venous occlusion plethysmography was used for FBF assessment. Sodium nitroprusside was infused at 3 and 10 ug/min each for 6 minutes per infusion into the brachial artery of the test arm. Measures were made in both arms concurrently. Change in the absolute FBF from Day 1 to Day 42 in response to sodium nitroprusside is the difference between absolute value of FBF in infused arm on Day 1 and Day 42 in response to sodium nitroprusside. PDPP Population. Only those participants with data available at the specified data points were analyzed. 99999 indicates standard deviation could not be calculated as a single participant was analyzed.
    End point type
    Secondary
    End point timeframe
    Day 1 to Day 42
    End point values
    		 Daprodustat Darbepoetin alfa
    Number of subjects analysed
    1
    2
    Units: ug/min
    arithmetic mean (standard deviation)
        3 ug/min
    -0.2560 ( 99999 )
    0.3844 ( 0.52197 )
        10 ug/min
    6.8103 ( 99999 )
    -0.2873 ( 1.11519 )
    No statistical analyses for this end point

    Secondary: Change in FBF ratio in response to NG-monomethyl arginine acetate (L-NMMA) (Day 1 to Day 42)

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    End point title
    		 Change in FBF ratio in response to NG-monomethyl arginine acetate (L-NMMA) (Day 1 to Day 42)
    End point description
    Venous occlusion plethysmography was used for FBF assessment. Effects on basal nitric oxide synthesis was assessed using L-NMMA at doses of 2 and 8 micromoles per minute (umol/min) each infused for 6 minutes into the brachial artery of the test arm. FBF ratio was defined as the ratio of a participant’s treatment (infused) arm value divided by the non-treatment (non-infused) arm value. The overall ratio was determined by taking the participant’s Day 42 FBF ratio and dividing by the Day 1 FBF ratio. Change in FBF ratio was the difference between daprodustat and darbepoetin alfa FBF ratio. PDPP Population. Only those participants with data available at the specified data points were analyzed. 99999 indicates standard deviation could not be calculated as a single participant was analyzed.
    End point type
    Secondary
    End point timeframe
    Day 1 to Day 42
    End point values
    		 Daprodustat, Darbepoetin alfa
    Number of subjects analysed
    1
    Units: Ratio
    arithmetic mean (standard deviation)
        2 umol/min
    -0.1598 ( 99999 )
        8 umol/min
    -0.3715 ( 99999 )
    No statistical analyses for this end point

    Secondary: Change in the absolute FBF from Day 1 to Day 42 in response to L-NMMA

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    End point title
    		 Change in the absolute FBF from Day 1 to Day 42 in response to L-NMMA
    End point description
    Venous occlusion plethysmography was used for FBF assessment. Effects on basal nitric oxide synthesis was assessed using L-NMMA at doses of 2 and 8 umol/min each infused for 6 minutes into the brachial artery of the test arm. Measures were made in both arms concurrently. Change in the absolute FBF from Day 1 to Day 42 in response to L-NMMA is the difference between absolute value of FBF in infused arm on Day 1 and Day 42 in response to L-NMMA. PDPP Population. Only those participants with data available at the specified data points were analyzed. 99999 indicates standard deviation could not be calculated as a single participant was analyzed.
    End point type
    Secondary
    End point timeframe
    Day 1 to Day 42
    End point values
    		 Daprodustat Darbepoetin alfa
    Number of subjects analysed
    1
    1
    Units: umol/min
    arithmetic mean (standard deviation)
        2 umol/min
    1.1508 ( 99999 )
    0.3558 ( 99999 )
        8 umol/min
    0.0974 ( 99999 )
    0.0399 ( 99999 )
    No statistical analyses for this end point

    Secondary: Change in FBF ratio in response to acetylcholine at Day 42 versus (vs) Day 1 in participants treated with daprodustat

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    End point title
    		 Change in FBF ratio in response to acetylcholine at Day 42 versus (vs) Day 1 in participants treated with daprodustat [2]
    End point description
    Venous occlusion plethysmography was used for FBF assessment. Acetylcholine was infused intra-arterially at 7.5, 15 and 30 ug/min each for 6 minutes per infusion. The Day 42 ratio was calculated by taking the participants Day 42 treatment (infused) arm and dividing by the Day 42 non-treatment (control) arm value. The Day 1 ratio was calculated by taking the participants Day 1 treatment (infused) arm and dividing by the Day 1 non-treatment (control) arm value. Change in FBF ratio from Day 1 to Day 42 was determined by taking the participants Day 42 ratio and dividing by the Day 1 ratio. PDPP Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles). 99999 indicates standard deviation could not be calculated as a single participant was analyzed.
    End point type
    Secondary
    End point timeframe
    Day 1 and Day 42
    Notes
    [2] - 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: There are no statistical data to report
    End point values
    		 Daprodustat
    Number of subjects analysed
    2
    Units: Ratio
    arithmetic mean (standard deviation)
        7.5 ug/min, n=2
    0.2744 ( 0.91996 )
        15 ug/min, n=1
    -0.8503 ( 99999 )
        30 ug/min, n=1
    0.5482 ( 99999 )
    No statistical analyses for this end point

    Secondary: Change in FBF ratio in response to sodium nitroprusside at Day 42 vs Day 1 in participants treated with daprodustat

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    End point title
    		 Change in FBF ratio in response to sodium nitroprusside at Day 42 vs Day 1 in participants treated with daprodustat [3]
    End point description
    Venous occlusion plethysmography was used for FBF assessment. Sodium nitroprusside was infused at 3 and 10 ug/min each for 6 minutes per infusion into the brachial artery of the test arm. The Day 42 ratio was calculated by taking the participants Day 42 treatment (infused) arm and dividing by the Day 42 non-treatment (control) arm value. The Day 1 ratio was calculated by taking the participants Day 1 treatment (infused) arm and dividing by the Day 1 non-treatment (control) arm value. Change in FBF ratio from Day 1 to Day 42 was determined by taking the participants Day 42 ratio and dividing by the Day 1 ratio. PDPP Population. Only those participants with data available at the specified data points were analyzed. 99999 indicates standard deviation could not be calculated as a single participant was analyzed.
    End point type
    Secondary
    End point timeframe
    Day 1 and Day 42
    Notes
    [3] - 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: There are no statistical data to report
    End point values
    		 Daprodustat
    Number of subjects analysed
    1
    Units: Ratio
    arithmetic mean (standard deviation)
        3 ug/min
    0.1618 ( 99999 )
        10 ug/min
    3.2651 ( 99999 )
    No statistical analyses for this end point

    Secondary: Change in FBF ratio in response to L-NMMA at Day 42 vs Day 1 in participants treated with daprodustat

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    End point title
    		 Change in FBF ratio in response to L-NMMA at Day 42 vs Day 1 in participants treated with daprodustat [4]
    End point description
    Venous occlusion plethysmography was used for FBF assessment. Effects on basal nitric oxide synthesis was assessed using L-NMMA at doses of 2 and 8 umol/min each infused for 6 minutes into the brachial artery of the test arm. The Day 42 ratio was calculated by taking the participants Day 42 treatment (infused) arm and dividing by the Day 42 non-treatment (control) arm value. The Day 1 ratio was calculated by taking the participants Day 1 treatment (infused) arm and dividing by the Day 1 non-treatment (control) arm value. Change in FBF ratio from Day 1 to Day 42 was determined by taking the participants Day 42 ratio and dividing by the Day 1 ratio. PDPP Population. Only those participants with data available at the specified data points were analyzed. 99999 indicates standard deviation could not be calculated as a single participant was analyzed.
    End point type
    Secondary
    End point timeframe
    Day 1 and Day 42
    Notes
    [4] - 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: There are no statistical data to report
    End point values
    		 Daprodustat
    Number of subjects analysed
    1
    Units: Ratio
    arithmetic mean (standard deviation)
        2 umol/min
    -0.3896 ( 99999 )
        8 umol/min
    -0.7216 ( 99999 )
    No statistical analyses for this end point

    Secondary: Change in FBF ratio in response to acetylcholine at Day 42 vs Day 1 in participants treated with darbepoetin alfa

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    End point title
    		 Change in FBF ratio in response to acetylcholine at Day 42 vs Day 1 in participants treated with darbepoetin alfa [5]
    End point description
    Venous occlusion plethysmography was used for FBF assessment. Acetylcholine was infused intra-arterially at 7.5, 15 and 30 ug/min each for 6 minutes per infusion. The Day 42 ratio was calculated by taking the participants Day 42 treatment (infused) arm and dividing by the Day 42 non-treatment (control) arm value. The Day 1 ratio was calculated by taking the participants Day 1 treatment (infused) arm and dividing by the Day 1 non-treatment (control) arm value. Change in FBF ratio from Day 1 to Day 42 was determined by taking the participants Day 42 ratio and dividing by the Day 1 ratio. PDPP Population
    End point type
    Secondary
    End point timeframe
    Day 1 and Day 42
    Notes
    [5] - 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: There are no statistical data to report
    End point values
    		 Darbepoetin alfa
    Number of subjects analysed
    2
    Units: Ratio
    arithmetic mean (standard deviation)
        7.5 ug/min
    -2.0376 ( 0.63291 )
        15 ug/min
    -1.4559 ( 0.01558 )
        30 ug/min
    -1.0652 ( 1.56389 )
    No statistical analyses for this end point

    Secondary: Change in FBF ratio in response to sodium nitroprusside at Day 42 vs Day 1 in participants treated with darbepoetin alfa

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    End point title
    		 Change in FBF ratio in response to sodium nitroprusside at Day 42 vs Day 1 in participants treated with darbepoetin alfa [6]
    End point description
    Venous occlusion plethysmography was used for FBF assessment. Sodium nitroprusside was infused at 3 and 10 ug/min each for 6 minutes per infusion into the brachial artery of the test arm. The Day 42 ratio was calculated by taking the participants Day 42 treatment (infused) arm and dividing by the Day 42 non-treatment (control) arm value. The Day 1 ratio was calculated by taking the participants Day 1 treatment (infused) arm and dividing by the Day 1 non-treatment (control) arm value. Change in FBF ratio from Day 1 to Day 42 was determined by taking the participants Day 42 ratio and dividing by the Day 1 ratio. PDPP Population.
    End point type
    Secondary
    End point timeframe
    Day 1 and Day 42
    Notes
    [6] - 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: There are no statistical data to report
    End point values
    		 Darbepoetin alfa
    Number of subjects analysed
    2
    Units: Ratio
    arithmetic mean (standard deviation)
        3 ug/min
    -0.7503 ( 0.26692 )
        10 ug/min
    -1.2405 ( 0.15366 )
    No statistical analyses for this end point

    Secondary: Change in FBF ratio in response to L-NMMA at Day 42 vs Day 1 in participants treated with darbepoetin alfa

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    End point title
    		 Change in FBF ratio in response to L-NMMA at Day 42 vs Day 1 in participants treated with darbepoetin alfa [7]
    End point description
    Venous occlusion plethysmography was used for FBF assessment. Effects on basal nitric oxide synthesis was assessed using L-NMMA at doses of 2 and 8 umol/min each infused for 6 minutes into the brachial artery of the test arm. The Day 42 ratio was calculated by taking the participants Day 42 treatment (infused) arm and dividing by the Day 42 non-treatment (control) arm value. The Day 1 ratio was calculated by taking the participants Day 1 treatment (infused) arm and dividing by the Day 1 non-treatment (control) arm value. Change in FBF ratio from Day 1 to Day 42 was determined by taking the participants Day 42 ratio and dividing by the Day 1 ratio. PDPP Population. Only those participants with data available at the specified data points were analyzed. 99999 indicates standard deviation could not be calculated as a single participant was analyzed.
    End point type
    Secondary
    End point timeframe
    Day 1 and Day 42
    Notes
    [7] - 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: There are no statistical data to report
    End point values
    		 Darbepoetin alfa
    Number of subjects analysed
    1
    Units: Ratio
    arithmetic mean (standard deviation)
        2 umol/min
    -0.081 ( 99999 )
        8 umol/min
    -0.1351 ( 99999 )
    No statistical analyses for this end point

    Secondary: Change in the absolute FBF in response to acetylcholine at Day 42 vs Day 1 in participants treated with daprodustat

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    End point title
    		 Change in the absolute FBF in response to acetylcholine at Day 42 vs Day 1 in participants treated with daprodustat [8]
    End point description
    Venous occlusion plethysmography was used for FBF assessment. Acetylcholine was infused intra-arterially at 7.5, 15 and 30 ug/min each for 6 minutes per infusion. Measures were made in both arms concurrently. Change in the absolute FBF in response to acetylcholine at Day 42 vs Day1 is the difference between absolute value of FBF in infused arm on Day 1 and Day 42 in response to acetylcholine in participants treated with daprodustat. PDPP Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles). 99999 indicates standard deviation could not be calculated as a single participant was analyzed.
    End point type
    Secondary
    End point timeframe
    Day 1 and Day 42
    Notes
    [8] - 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: There are no statistical data to report
    End point values
    		 Daprodustat
    Number of subjects analysed
    2
    Units: ug/min
    arithmetic mean (standard deviation)
        7.5 ug/min, n=2
    8.3180 ( 4.50592 )
        15 ug/min, n=1
    -4.6374 ( 99999 )
        30 ug/min, n=1
    -2.6735 ( 99999 )
    No statistical analyses for this end point

    Secondary: Change in the absolute FBF in response to sodium nitroprusside at Day 42 vs Day 1 in participants treated with daprodustat

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    End point title
    		 Change in the absolute FBF in response to sodium nitroprusside at Day 42 vs Day 1 in participants treated with daprodustat [9]
    End point description
    Venous occlusion plethysmography was used for FBF assessment. Sodium nitroprusside was infused at 3 and 10 ug/min each for 6 minutes per infusion into the brachial artery of the test arm. Measures were made in both arms concurrently. Change in the absolute FBF in response to sodium nitroprusside at Day 42 vs Day 1 is the difference between absolute value of FBF in infused arm on Day 1 and Day 42 in response to sodium nitroprusside in participants treated with daprodustat. PDPP Population. Only those participants with data available at the specified data points were analyzed. 99999 indicates standard deviation could not be calculated as a single participant was analyzed.
    End point type
    Secondary
    End point timeframe
    Day 1 and Day 42
    Notes
    [9] - 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: There are no statistical data to report
    End point values
    		 Daprodustat
    Number of subjects analysed
    1
    Units: ug/min
    arithmetic mean (standard deviation)
        3 ug/min
    -0.2560 ( 99999 )
        10 ug/min
    6.8103 ( 99999 )
    No statistical analyses for this end point

    Secondary: Change in the absolute FBF in response to L-NMMA at Day 42 vs Day 1 in participants treated with daprodustat

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    End point title
    		 Change in the absolute FBF in response to L-NMMA at Day 42 vs Day 1 in participants treated with daprodustat [10]
    End point description
    Venous occlusion plethysmography was used for FBF assessment. Effects on basal nitric oxide synthesis was assessed using L-NMMA at doses of 2 and 8 umol/min each infused for 6 minutes into the brachial artery of the test arm. Measures were made in both arms concurrently. Change in the absolute FBF in response to L-NMMA at Day 42 vs Day 1 is the difference between absolute value of FBF in infused arm on Day 1 and Day 42 in response to L-NMMA in participants treated with daprodustat. PDPP Population. Only those participants with data available at the specified data points were analyzed. 99999 indicates standard deviation could not be calculated as a single participant was analyzed.
    End point type
    Secondary
    End point timeframe
    Day 1 and Day 42
    Notes
    [10] - 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: There are no statistical data to report
    End point values
    		 Daprodustat
    Number of subjects analysed
    1
    Units: umol/min
    arithmetic mean (standard deviation)
        2 umol/min
    1.1508 ( 99999 )
        8 umol/min
    0.0974 ( 99999 )
    No statistical analyses for this end point

    Secondary: Change in the absolute FBF in response to acetylcholine at Day 42 vs Day 1 in participants treated with darbepoetin alfa

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    End point title
    		 Change in the absolute FBF in response to acetylcholine at Day 42 vs Day 1 in participants treated with darbepoetin alfa [11]
    End point description
    Venous occlusion plethysmography was used for FBF assessment. Acetylcholine was infused intra-arterially at 7.5, 15 and 30 ug/min each for 6 minutes per infusion. Measures were made in both arms concurrently. Change in the absolute FBF in response to acetylcholine at Day 42 vs Day1 is the difference between absolute value of FBF in infused arm on Day 1 and Day 42 in response to acetylcholine in participants treated with darbepoetin alfa. PDPP Population.
    End point type
    Secondary
    End point timeframe
    Day 1 and Day 42
    Notes
    [11] - 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: There are no statistical data to report
    End point values
    		 Darbepoetin alfa
    Number of subjects analysed
    2
    Units: ug/min
    arithmetic mean (standard deviation)
        7.5 ug/min
    -6.0360 ( 3.09976 )
        15 ug/min
    -8.8299 ( 9.98143 )
        30 ug/min
    -4.5121 ( 5.66731 )
    No statistical analyses for this end point

    Secondary: Change in the absolute FBF in response to sodium nitroprusside at Day 42 vs Day 1 in participants treated with darbepoetin alfa

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    End point title
    		 Change in the absolute FBF in response to sodium nitroprusside at Day 42 vs Day 1 in participants treated with darbepoetin alfa [12]
    End point description
    Venous occlusion plethysmography was used for FBF assessment. Sodium nitroprusside was infused at 3 and 10 ug/min each for 6 minutes per infusion into the brachial artery of the test arm. Measures were made in both arms concurrently. Change in the absolute FBF in response to sodium nitroprusside at Day 42 vs Day 1 is the difference between absolute value of FBF in infused arm on Day 1 and Day 42 in response to sodium nitroprusside in participants treated with darbepoetin alfa. PDPP Population.
    End point type
    Secondary
    End point timeframe
    Day 1 and Day 42
    Notes
    [12] - 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: There are no statistical data to report
    End point values
    		 Darbepoetin alfa
    Number of subjects analysed
    2
    Units: ug/min
    arithmetic mean (standard deviation)
        3 ug/min
    0.3844 ( 0.52197 )
        10 ug/min
    -0.2873 ( 1.11519 )
    No statistical analyses for this end point

    Secondary: Change in the absolute FBF in response to L-NMMA at Day 42 vs Day 1 in participants treated with darbepoetin alfa

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    End point title
    		 Change in the absolute FBF in response to L-NMMA at Day 42 vs Day 1 in participants treated with darbepoetin alfa [13]
    End point description
    Venous occlusion plethysmography was used for FBF assessment. Effects on basal nitric oxide synthesis was assessed using L-NMMA at doses of 2 and 8 umol/min each infused for 6 minutes into the brachial artery of the test arm. Measures were made in both arms concurrently. Change in the absolute FBF in response to L-NMMA at Day 42 vs Day 1 is the difference between absolute value of FBF in infused arm on Day 1 and Day 42 in response to L-NMMA in participants treated with darbepoetin alfa. PDPP Population. Only those participants with data available at the specified data points were analyzed. 99999 indicates standard deviation could not be calculated as a single participant was analyzed.
    End point type
    Secondary
    End point timeframe
    Day 1 and Day 42
    Notes
    [13] - 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: There are no statistical data to report
    End point values
    		 Darbepoetin alfa
    Number of subjects analysed
    1
    Units: umol/min
    arithmetic mean (standard deviation)
        2 umol/min
    0.3558 ( 99999 )
        8 umol/min
    0.0399 ( 99999 )
    No statistical analyses for this end point

    Secondary: Change in Augmentation index (AIx) from Day 1 to 42

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    End point title
    		 Change in Augmentation index (AIx) from Day 1 to 42
    End point description
    Pulse wave analysis (PWA) is a reproducible, noninvasive method for assessing AIx (a measure of the contribution that wave reflection makes to the arterial pressure waveform). The amplitude and timing of the reflected wave ultimately depends on the stiffness of the small (pre-resistance) vessels and large arteries, and thus, AIx provides a measure of systemic arterial stiffness. A high-fidelity micro manometer was used to obtain accurate readings of the peripheral pressure waveforms by flattening, but not occluding, the radial artery of the dominant arm using gentle pressure. AIx was defined as the augmentation (difference between systolic peaks) expressed as a percentage of the overall pulse pressure. Data for change in AIx from Day 1 to 42 was presented. PDPP Population.
    End point type
    Secondary
    End point timeframe
    Day 1 to Day 42
    End point values
    		 Daprodustat Darbepoetin alfa
    Number of subjects analysed
    2
    2
    Units: Percentage
        arithmetic mean (standard deviation)
    -3.000 ( 0.0000 )
    -4.000 ( 2.8284 )
    No statistical analyses for this end point

    Secondary: Change in pulse wave velocity (PWV) from Day 1 to Day 42

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    End point title
    		 Change in pulse wave velocity (PWV) from Day 1 to Day 42
    End point description
    PWV was assessed with a high-fidelity micro manometer which was used to obtain accurate readings of the peripheral pressure waveforms by flattening, but not occluding, the carotid and femoral arteries as the two points of measure. Data for change in PWV from Day 1 to 42 was presented. PDPP Population.
    End point type
    Secondary
    End point timeframe
    Day 1 to Day 42
    End point values
    		 Daprodustat Darbepoetin alfa
    Number of subjects analysed
    2
    2
    Units: meters per second (m/sec)
        arithmetic mean (standard deviation)
    2.075 ( 1.4496 )
    0.100 ( 0.2828 )
    No statistical analyses for this end point

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

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    End point title
    		 Number of participants with any adverse events (AEs) and serious adverse events (SAEs)
    End point description
    An AE is any untoward medical occurrence in a clinical study participants, 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. Safety Population includes all randomized participants who received at least one dose of study treatment.
    End point type
    Secondary
    End point timeframe
    Up to 59 days
    End point values
    		 Daprodustat Darbepoetin alfa
    Number of subjects analysed
    2
    3
    Units: Participants
        Any AEs
    0
    1
        Any SAEs
    0
    0
    No statistical analyses for this end point

    Secondary: Number of participants with any AE of special interest (AESI)

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    End point title
    		 Number of participants with any AE of special interest (AESI)
    End point description
    AESIs were identified based on non-clinical studies with daprodustat, clinical experience with recombinant human erythropoietins (rhEPOs), and current information regarding hypoxia-inducible factor (HIF)-regulated pathways in mediating hypoxia-associated pathophysiology. The AESIs for daprodustat were identified as follows: Thrombosis and/or tissue ischemia secondary to excessive erythropoiesis; Death, MI, stroke, heart failure, thromboembolic events, thrombosis of vascular access; Cardiomyopathy; Pulmonary artery hypertension; Cancer-related mortality and tumor progression and recurrence Esophageal and gastric erosions; Proliferative retinopathy, macular edema, choroidal neovascularization; Exacerbation of rheumatoid arthritis and Worsening of hypertension. Safety Population.
    End point type
    Secondary
    End point timeframe
    Up to 59 days
    End point values
    		 Daprodustat Darbepoetin alfa
    Number of subjects analysed
    2
    3
    Units: Participants
    0
    0
    No statistical analyses for this end point

    Secondary: Number of participants discontinuing the randomized study treatment

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    End point title
    		 Number of participants discontinuing the randomized study treatment
    End point description
    Number of participants who discontinued the randomized study treatment were assessed. Safety Population.
    End point type
    Secondary
    End point timeframe
    Up to Day 42
    End point values
    		 Daprodustat Darbepoetin alfa
    Number of subjects analysed
    2
    3
    Units: Participants
    0
    0
    No statistical analyses for this end point

    Other pre-specified: Absolute values of diastolic blood pressure (DBP) and systolic blood pressure (SBP)

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    End point title
    		 Absolute values of diastolic blood pressure (DBP) and systolic blood pressure (SBP)
    End point description
    DBP and SBP were measured in a semi-supine position with a completely automated device preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions. Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
    End point type
    Other pre-specified
    End point timeframe
    Days 1, 14, 28, 42 and 59
    End point values
    		 Daprodustat Darbepoetin alfa
    Number of subjects analysed
    2
    3
    Units: millimeters of mercury (mmHg)
    arithmetic mean (standard deviation)
        DBP, Day 1, n=2, 3
    73.5 ( 13.44 )
    69.3 ( 13.05 )
        DBP, Day 14, n=2, 3
    67.0 ( 5.66 )
    74.3 ( 13.05 )
        DBP, Day 28, n=2, 3
    73.5 ( 7.78 )
    79.3 ( 25.54 )
        DBP, Day 42, n=2, 2
    76.0 ( 9.90 )
    73.0 ( 8.49 )
        DBP, Day 59, n=2, 3
    69.5 ( 9.19 )
    82.7 ( 18.15 )
        SBP, Day 1, n=2, 3
    144.0 ( 43.84 )
    134.3 ( 18.34 )
        SBP, Day 14, n=2, 3
    130.0 ( 28.28 )
    127.7 ( 23.25 )
        SBP, Day 28, n=2, 3
    135.5 ( 12.02 )
    147.3 ( 39.63 )
        SBP, Day 42, n=2, 2
    145.5 ( 33.23 )
    148.0 ( 45.25 )
        SBP, Day 59, n=2, 3
    135.5 ( 31.82 )
    142.3 ( 29.14 )
    No statistical analyses for this end point

    Other pre-specified: Change from Baseline in DBP and SBP

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    End point title
    		 Change from Baseline in DBP and SBP
    End point description
    DBP and SBP were measured in a semi-supine position with a completely automated device preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline value (Day 1) is the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value. Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
    End point type
    Other pre-specified
    End point timeframe
    Baseline (Day 1) and at Days 14, 28, 42 and 59
    End point values
    		 Daprodustat Darbepoetin alfa
    Number of subjects analysed
    2
    3
    Units: mmHg
    arithmetic mean (standard deviation)
        DBP, Day 14, n=2, 3
    -6.5 ( 7.78 )
    5.0 ( 0.00 )
        DBP, Day 28, n=2, 3
    0.0 ( 21.21 )
    10.0 ( 13.00 )
        DBP, Day 42, n=2, 2
    2.5 ( 3.54 )
    10.5 ( 0.71 )
        DBP, Day 59, n=2, 3
    -4.0 ( 4.24 )
    13.3 ( 5.13 )
        SBP, Day 14, n=2, 3
    -14.0 ( 15.56 )
    -6.7 ( 4.93 )
        SBP, Day 28, n=2, 3
    -8.5 ( 31.82 )
    13.0 ( 38.43 )
        SBP, Day 42, n=2, 2
    1.5 ( 10.61 )
    10.5 ( 20.51 )
        SBP, Day 59, n=2, 3
    -8.5 ( 12.02 )
    8.0 ( 24.02 )
    No statistical analyses for this end point

    Other pre-specified: Absolute values of electrocardiogram (ECG) mean heart rate

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    End point title
    		 Absolute values of electrocardiogram (ECG) mean heart rate
    End point description
    Full 12-lead ECG were recorded with the participant in a semi-supine position to measure heart rate. Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
    End point type
    Other pre-specified
    End point timeframe
    Days 1, 42 and 59
    End point values
    		 Daprodustat Darbepoetin alfa
    Number of subjects analysed
    2
    3
    Units: Beats per minute
    arithmetic mean (standard deviation)
        Day 1, n=2, 3
    69.0 ( 2.83 )
    70.0 ( 14.11 )
        Day 42, n=2, 2
    61.0 ( 14.14 )
    62.0 ( 9.90 )
        Day 59, n=2, 3
    71.5 ( 9.19 )
    73.7 ( 20.03 )
    No statistical analyses for this end point

    Other pre-specified: 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
    Full 12-lead ECG were recorded with the participant in a semi-supine position to measure heart rate. Baseline value (Day 1) is the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value. Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
    End point type
    Other pre-specified
    End point timeframe
    Baseline (Day 1) and at Days 42 and 59
    End point values
    		 Daprodustat Darbepoetin alfa
    Number of subjects analysed
    2
    3
    Units: Beats per minute
    arithmetic mean (standard deviation)
        Day 42, n=2, 2
    -8.0 ( 11.31 )
    -0.5 ( 2.12 )
        Day 59, n=2, 3
    2.5 ( 12.02 )
    3.7 ( 9.50 )
    No statistical analyses for this end point

    Other pre-specified: Absolute values of ECG parameters- PR interval, QRS interval, and QT interval and QT interval corrected for heart rate using Bazett’s formula (QTcB)

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    End point title
    		 Absolute values of ECG parameters- PR interval, QRS interval, and QT interval and QT interval corrected for heart rate using Bazett’s formula (QTcB)
    End point description
    Full 12-lead ECGs were recorded with the participant in a semi-supine position to measure PR interval, QRS duration, QT interval and QTcB, calculated (machine read or manually). Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
    End point type
    Other pre-specified
    End point timeframe
    Days 1, 42 and 59
    End point values
    		 Daprodustat Darbepoetin alfa
    Number of subjects analysed
    2
    3
    Units: Milliseconds
    arithmetic mean (standard deviation)
        PR Interval, Day 1, n=2, 3
    139.0 ( 1.41 )
    181.7 ( 23.16 )
        PR Interval, Day 42, n=2, 2
    146.5 ( 7.78 )
    192.5 ( 10.61 )
        PR Interval, Day 59, n=2, 3
    146.5 ( 2.12 )
    182.0 ( 18.00 )
        QRS Duration, Day 1, n=2, 3
    87.0 ( 7.07 )
    94.7 ( 5.03 )
        QRS Duration, Day 42, n=2, 2
    88.5 ( 9.19 )
    96.5 ( 10.61 )
        QRS Duration, Day 59, n=2, 3
    87.0 ( 9.90 )
    95.3 ( 7.02 )
        QT Interval, Day 1, n=2, 3
    395.5 ( 6.36 )
    391.3 ( 14.47 )
        QT Interval, Day 42, n=2, 2
    413.5 ( 20.51 )
    388.0 ( 11.31 )
        QT Interval, Day 59, n=2, 3
    383.5 ( 44.55 )
    382.3 ( 33.71 )
        QTcB Interval, Day 1, n=2, 3
    424.0 ( 1.41 )
    420.7 ( 31.79 )
        QTcB Interval, Day 42, n=2, 2
    414.5 ( 27.58 )
    393.0 ( 19.80 )
        QTcB Interval, Day 59, n=2, 3
    416.5 ( 21.92 )
    417.3 ( 33.32 )
    No statistical analyses for this end point

    Other pre-specified: Change from Baseline in ECG parameters- PR interval, QRS duration, and QT interval and QTcB

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    End point title
    		 Change from Baseline in ECG parameters- PR interval, QRS duration, and QT interval and QTcB
    End point description
    Full 12-lead ECGs were recorded with the participant in a semi-supine position to measure PR interval, QRS duration, QT (uncorrected) interval and QTcB, calculated (machine read or manually). Baseline value (Day 1) is the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value. Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
    End point type
    Other pre-specified
    End point timeframe
    Baseline (Day 1) and at Days 42 and 59
    End point values
    		 Daprodustat Darbepoetin alfa
    Number of subjects analysed
    2
    3
    Units: Milliseconds
    arithmetic mean (standard deviation)
        PR Interval, Day 42, n=2, 2
    7.5 ( 6.36 )
    -2.0 ( 19.80 )
        PR Interval, Day 59, n=2, 3
    7.5 ( 0.71 )
    0.3 ( 16.86 )
        QRS Duration, Day 42, n=2, 2
    1.5 ( 2.12 )
    1.5 ( 3.54 )
        QRS Duration, Day 59, n=2, 3
    0.0 ( 2.83 )
    0.7 ( 2.31 )
        QT Interval, Day 42, n=2, 2
    18.0 ( 14.14 )
    -7.0 ( 7.07 )
        QT Interval, Day 59, n=2, 3
    -12.0 ( 50.91 )
    -9.0 ( 19.67 )
        QTcB Interval, Day 42, n=2, 2
    -9.5 ( 26.16 )
    -9.5 ( 13.44 )
        QTcB Interval, Day 59, n=2, 3
    -7.5 ( 20.51 )
    -3.3 ( 8.02 )
    No statistical analyses for this end point

    Other pre-specified: Absolute values of the hematology parameters of platelet count, white blood cell (WBC) count (Absolute), basophils, eosinophils, lymphocytes, monocytes and neutrophils

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    End point title
    		 Absolute values of the hematology parameters of platelet count, white blood cell (WBC) count (Absolute), basophils, eosinophils, lymphocytes, monocytes and neutrophils
    End point description
    Blood samples were collected for the analysis of hematology parameters including platelet count, leukocytes, basophils, eosinophils, lymphocytes, monocytes and neutrophils. Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
    End point type
    Other pre-specified
    End point timeframe
    Days 1, 42 and 59
    End point values
    		 Daprodustat Darbepoetin alfa
    Number of subjects analysed
    2
    3
    Units: Giga cells per Liter
    arithmetic mean (standard deviation)
        Platelet count, Day 1, n=2, 3
    199.0 ( 63.64 )
    191.7 ( 68.13 )
        Platelet count, Day 42, n=2, 2
    203.5 ( 57.28 )
    121.5 ( 13.44 )
        Platelet count, Day 59, n=2, 3
    193.0 ( 41.01 )
    50.08 ( 50.08 )
        Leukocytes, Day 1, n=2, 3
    5.05 ( 1.202 )
    6.30 ( 2.117 )
        Leukocytes, Day 42, n=2, 2
    6.05 ( 2.616 )
    5.75 ( 2.051 )
        Leukocytes, Day 59, n=2, 3
    5.30 ( 1.414 )
    7.20 ( 2.261 )
        Basophils, Day 1, n=2, 3
    0.045 ( 0.0212 )
    0.057 ( 0.0503 )
        Basophils, Day 42, n=2, 2
    0.045 ( 0.0212 )
    0.045 ( 0.0212 )
        Basophils, Day 59, n=2, 3
    0.035 ( 0.0071 )
    0.050 ( 0.0400 )
        Eosinophils, Day 1, n=2, 3
    0.295 ( 0.1485 )
    0.230 ( 0.1353 )
        Eosinophils, Day 42, n=2, 2
    0.300 ( 0.1980 )
    0.175 ( 0.0778 )
        Eosinophils, Day 59, n=2, 3
    0.245 ( 0.1485 )
    0.220 ( 0.1311 )
        Lymphocytes, Day 1, n=2, 3
    1.160 ( 0.2404 )
    2.037 ( 1.4989 )
        Lymphocytes, Day 42, n=2, 2
    1.275 ( 0.2616 )
    1.150 ( 0.4808 )
        Lymphocytes, Day 59, n=2, 3
    0.785 ( 0.3748 )
    2.033 ( 1.3580 )
        Monocytes, Day 1, n=2, 3
    0.400 ( 0.0566 )
    0.607 ( 0.3147 )
        Monocytes, Day 42, n=2, 2
    0.415 ( 0.0071 )
    0.445 ( 0.2192 )
        Monocytes, Day 59, n=2, 3
    0.415 ( 0.0778 )
    0.563 ( 0.2574 )
        Neutrophils, Day 1, n=2, 3
    3.160 ( 1.3576 )
    3.387 ( 0.2053 )
        Neutrophils, Day 42, n=2, 2
    4.010 ( 2.6870 )
    3.970 ( 2.1920 )
        Neutrophils, Day 59, n=2, 3
    3.825 ( 1.0112 )
    4.343 ( 1.0060 )
    No statistical analyses for this end point

    Other pre-specified: Change from Baseline in hematology parameters of platelet count, WBC count (Absolute), basophils, eosinophils, lymphocytes, monocytes and neutrophils

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    End point title
    		 Change from Baseline in hematology parameters of platelet count, WBC count (Absolute), basophils, eosinophils, lymphocytes, monocytes and neutrophils
    End point description
    Blood samples were collected for the analysis of hematology parameters including platelet count, leukocytes, basophils, eosinophils, lymphocytes, monocytes and neutrophils. Baseline value (Day 1) is the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value. Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
    End point type
    Other pre-specified
    End point timeframe
    Baseline (Day 1) and at Days 42 and 59
    End point values
    		 Daprodustat Darbepoetin alfa
    Number of subjects analysed
    2
    3
    Units: Giga cells per Liter
    arithmetic mean (standard deviation)
        Platelet count, Day 42, n=2, 2
    4.5 ( 6.36 )
    -51.0 ( 70.71 )
        Platelet count, Day 59, n=2, 3
    -6.0 ( 22.63 )
    -26.3 ( 51.98 )
        Leukocytes, Day 42, n=2, 2
    1.00 ( 1.414 )
    0.65 ( 2.616 )
        Leukocytes, Day 59, n=2, 3
    0.25 ( 0.212 )
    0.90 ( 1.054 )
        Basophils, Day 42, n=2, 2
    0.000 ( 0.0000 )
    0.015 ( 0.0071 )
        Basophils, Day 59, n=2, 3
    -0.010 ( 0.0283 )
    -0.007 ( 0.0115 )
        Eosinophils, Day 42, n=2, 2
    0.005 ( 0.0495 )
    0.015 ( 0.0071 )
        Eosinophils, Day 59, n=2, 3
    -0.050 ( 0.0000 )
    -0.010 ( 0.0100 )
        Lymphocytes, Day 42, n=2, 2
    0.115 ( 0.0212 )
    -0.040 ( 0.0424 )
        Lymphocytes, Day 59, n=2, 3
    -0.375 ( 0.6152 )
    -0.003 ( 0.1443 )
        Monocytes, Day 42, n=2, 2
    0.015 ( 0.0636 )
    0.020 ( 0.2263 )
        Monocytes, Day 59, n=2, 3
    0.015 ( 0.0212 )
    -0.043 ( 0.0586 )
        Neutrophils, Day 42, n=2, 2
    0.850 ( 1.3294 )
    0.670 ( 2.3900 )
        Neutrophils, Day 59, n=2, 3
    0.665 ( 0.3465 )
    0.957 ( 1.0929 )
    No statistical analyses for this end point

    Other pre-specified: Absolute values of the hematology parameter of red blood cell (RBC) count and reticulocyte count (RC)

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    End point title
    		 Absolute values of the hematology parameter of red blood cell (RBC) count and reticulocyte count (RC)
    End point description
    Blood samples were collected for the analysis of hematology parameters including RBC count and RC. Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
    End point type
    Other pre-specified
    End point timeframe
    Days 1, 42 and 59
    End point values
    		 Daprodustat Darbepoetin alfa
    Number of subjects analysed
    2
    3
    Units: Trillion cells per liter
    arithmetic mean (standard deviation)
        RBC, Day 1, n=2, 3
    3.45 ( 0.354 )
    3.20 ( 0.300 )
        RBC, Day 42, n=2, 2
    3.30 ( 0.283 )
    3.65 ( 0.071 )
        RBC, Day 59, n=2, 3
    3.35 ( 0.354 )
    3.63 ( 0.493 )
        RC, Day 1, n=2, 3
    0.04090 ( 0.018102 )
    0.06090 ( 0.038112 )
        RC, Day 42, n=2, 2
    0.04610 ( 0.023052 )
    0.07970 ( 0.057983 )
        RC, Day 59, n=2, 3
    0.03490 ( 0.014708 )
    0.04580 ( 0.049537 )
    No statistical analyses for this end point

    Other pre-specified: Change from Baseline in hematology parameters of RBC count and RC

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    End point title
    		 Change from Baseline in hematology parameters of RBC count and RC
    End point description
    Blood samples were collected for the analysis of hematology parameters including RBC count and RC. Baseline value (Day 1) is the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value. Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
    End point type
    Other pre-specified
    End point timeframe
    Baseline (Day 1) and at Days 42 and 59
    End point values
    		 Daprodustat Darbepoetin alfa
    Number of subjects analysed
    2
    3
    Units: Trillion cells per liter
    arithmetic mean (standard deviation)
        RBC, Day 42, n=2, 2
    -0.15 ( 0.071 )
    0.60 ( 0.141 )
        RBC, Day 59, n=2, 3
    -0.10 ( 0.000 )
    0.43 ( 0.252 )
        RC, Day 42, n=2, 2
    0.00520 ( 0.004950 )
    0.00815 ( 0.010819 )
        RC, Day 59, n=2, 3
    -0.00600 ( 0.003394 )
    -0.01510 ( 0.011467 )
    No statistical analyses for this end point

    Other pre-specified: Absolute values of the hematology parameters of hemoglobin and Mean Corpuscle Hemoglobin concentration (MCHC)

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    End point title
    		 Absolute values of the hematology parameters of hemoglobin and Mean Corpuscle Hemoglobin concentration (MCHC)
    End point description
    Blood samples were collected for the analysis of hematology parameters including hemoglobin and MCHC. Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
    End point type
    Other pre-specified
    End point timeframe
    Days 1, 42 and 59
    End point values
    		 Daprodustat Darbepoetin alfa
    Number of subjects analysed
    2
    3
    Units: Grams per deciliter
    arithmetic mean (standard deviation)
        Hemoglobin, Day 1, n=2, 3
    10.60 ( 0.849 )
    9.77 ( 0.586 )
        Hemoglobin, Day 42, n=2, 2
    10.45 ( 0.778 )
    11.40 ( 0.424 )
        Hemoglobin, Day 59, n=2, 3
    10.40 ( 0.849 )
    11.27 ( 1.002 )
        MCHC, Day 1, n=2, 3
    34.10 ( 0.000 )
    34.23 ( 0.351 )
        MCHC, Day 42, n=2, 2
    34.10 ( 0.141 )
    33.75 ( 1.909 )
        MCHC, Day 59, n=2, 3
    34.00 ( 0.141 )
    34.33 ( 1.447 )
    No statistical analyses for this end point

    Other pre-specified: Change from Baseline in hematology parameters- Hemoglobin and MCHC

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    End point title
    		 Change from Baseline in hematology parameters- Hemoglobin and MCHC
    End point description
    Blood samples were collected for the analysis of hematology parameters including hemoglobin and MCHC. Baseline value (Day 1) is the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value. Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
    End point type
    Other pre-specified
    End point timeframe
    Baseline (Day 1) and at Days 42 and 59
    End point values
    		 Daprodustat Darbepoetin alfa
    Number of subjects analysed
    2
    3
    Units: Grams per deciliter
    arithmetic mean (standard deviation)
        Hemoglobin, Day 42, n=2, 2
    -0.15 ( 0.071 )
    1.85 ( 0.212 )
        Hemoglobin, Day 59, n=2, 3
    -0.20 ( 0.000 )
    1.50 ( 0.520 )
        MCHC, Day 42, n=2, 2
    0.00 ( 0.141 )
    -0.65 ( 1.626 )
        MCHC, Day 59, n=2, 3
    -0.10 ( 0.141 )
    0.10 ( 1.127 )
    No statistical analyses for this end point

    Other pre-specified: Absolute values of hematology parameter: hematocrit

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    End point title
    		 Absolute values of hematology parameter: hematocrit
    End point description
    Blood samples were collected for the analysis of hematology parameters including hematocrit. Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
    End point type
    Other pre-specified
    End point timeframe
    Days 1, 42 and 59
    End point values
    		 Daprodustat Darbepoetin alfa
    Number of subjects analysed
    2
    3
    Units: Proportion of red blood cells in blood
    arithmetic mean (standard deviation)
        Day 1, n=2, 3
    0.3105 ( 0.02616 )
    0.2850 ( 0.01769 )
        Day 42, n=2, 2
    0.3065 ( 0.02475 )
    0.3385 ( 0.00636 )
        Day 59, n=2, 3
    0.3065 ( 0.02475 )
    0.3277 ( 0.03412 )
    No statistical analyses for this end point

    Other pre-specified: Change from Baseline in hematology parameter: hematocrit

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    End point title
    		 Change from Baseline in hematology parameter: hematocrit
    End point description
    Blood samples were collected for the analysis of hematology parameters including hematocrit. Baseline value (Day 1) is the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value. Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
    End point type
    Other pre-specified
    End point timeframe
    Baseline (Day 1) and at Days 42 and 59
    End point values
    		 Daprodustat Darbepoetin alfa
    Number of subjects analysed
    2
    3
    Units: Proportion of red blood cells in blood
    arithmetic mean (standard deviation)
        Day 42, n=2, 2
    -0.0040 ( 0.00141 )
    0.0615 ( 0.02192 )
        Day 59, n=2, 3
    -0.0040 ( 0.00141 )
    0.0427 ( 0.02212 )
    No statistical analyses for this end point

    Other pre-specified: Absolute values of hematology parameter of red blood cell distribution width (RDW)

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    End point title
    		 Absolute values of hematology parameter of red blood cell distribution width (RDW)
    End point description
    Blood samples were collected for the analysis of hematology parameters including RDW. Baseline value (Day 1) is the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
    End point type
    Other pre-specified
    End point timeframe
    Days 1, 42 and 59
    End point values
    		 Daprodustat Darbepoetin alfa
    Number of subjects analysed
    2
    3
    Units: Percentage of width
    arithmetic mean (standard deviation)
        Day 1, n=2, 3
    0.3105 ( 0.02616 )
    0.2850 ( 0.01769 )
        Day 42, n=2, 2
    13.45 ( 0.212 )
    14.00 ( 0.424 )
        Day 59, n=2, 3
    13.20 ( 0.141 )
    13.70 ( 0.200 )
    No statistical analyses for this end point

    Other pre-specified: Change from Baseline in RDW

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    End point title
    		 Change from Baseline in RDW
    End point description
    Blood samples were collected for the analysis of hematology parameters including RDW. Baseline value (Day 1) is the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value. Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
    End point type
    Other pre-specified
    End point timeframe
    Baseline (Day 1) and at Days 42 and 59
    End point values
    		 Daprodustat Darbepoetin alfa
    Number of subjects analysed
    2
    3
    Units: Percentage of width
    arithmetic mean (standard deviation)
        Day 42, n=2, 2
    0.00 ( 0.424 )
    1.15 ( 0.636 )
        Day 59, n=2, 3
    -0.25 ( 0.354 )
    0.70 ( 0.436 )
    No statistical analyses for this end point

    Other pre-specified: Absolute values of the hematology parameter of mean corpuscular hemoglobin (MCH)

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    End point title
    		 Absolute values of the hematology parameter of mean corpuscular hemoglobin (MCH)
    End point description
    Blood samples were collected for the analysis of hematology parameters including MCH. Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
    End point type
    Other pre-specified
    End point timeframe
    Days 1, 42 and 59
    End point values
    		 Daprodustat Darbepoetin alfa
    Number of subjects analysed
    2
    3
    Units: Picograms
    arithmetic mean (standard deviation)
        Day 1, n=2, 3
    30.95 ( 0.354 )
    30.67 ( 1.457 )
        Day 42, n=2, 2
    31.40 ( 0.424 )
    31.40 ( 0.707 )
        Day 59, n=2, 3
    31.10 ( 0.141 )
    30.93 ( 1.716 )
    No statistical analyses for this end point

    Other pre-specified: Change from Baseline in hematology parameter of MCH

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    End point title
    		 Change from Baseline in hematology parameter of MCH
    End point description
    Blood samples were collected for the analysis of hematology parameters including MCH. Baseline value (Day 1) is the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value. Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
    End point type
    Other pre-specified
    End point timeframe
    Baseline (Day 1) and at Days 42 and 59
    End point values
    		 Daprodustat Darbepoetin alfa
    Number of subjects analysed
    2
    3
    Units: Picograms
    arithmetic mean (standard deviation)
        Day 42, n=2, 2
    0.45 ( 0.071 )
    -0.10 ( 0.990 )
        Day 59, n=2, 3
    0.15 ( 0.212 )
    0.27 ( 0.862 )
    No statistical analyses for this end point

    Other pre-specified: Absolute values of the hematology parameter of mean corpuscular volume (MCV)

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    End point title
    		 Absolute values of the hematology parameter of mean corpuscular volume (MCV)
    End point description
    Blood samples were collected for the analysis of hematology parameters including MCV. Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
    End point type
    Other pre-specified
    End point timeframe
    Days 1, 42 and 59
    End point values
    		 Daprodustat Darbepoetin alfa
    Number of subjects analysed
    2
    3
    Units: Femtoliters
    arithmetic mean (standard deviation)
        Day 1, n=2, 3
    91.0 ( 1.41 )
    89.7 ( 3.51 )
        Day 42, n=2, 2
    92.0 ( 1.41 )
    93.0 ( 2.83 )
        Day 59, n=2, 3
    91.5 ( 0.71 )
    90.0 ( 3.00 )
    No statistical analyses for this end point

    Other pre-specified: Change from Baseline in hematology parameter of MCV

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    End point title
    		 Change from Baseline in hematology parameter of MCV
    End point description
    Blood samples were collected for the analysis of hematology parameters including MCV. Baseline value (Day 1) is the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value. Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
    End point type
    Other pre-specified
    End point timeframe
    Baseline (Day 1) and at Days 42 and 59
    End point values
    		 Daprodustat Darbepoetin alfa
    Number of subjects analysed
    2
    3
    Units: Femtoliters
    arithmetic mean (standard deviation)
        Day 42, n=2, 2
    1.0 ( 0.00 )
    1.5 ( 0.71 )
        Day 59, n=2, 3
    0.5 ( 0.71 )
    0.3 ( 0.58 )
    No statistical analyses for this end point

    Other pre-specified: Absolute values of clinical chemistry parameters of sodium, potassium, carbon-dioxide (total), chloride, glucose and urea

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    End point title
    		 Absolute values of clinical chemistry parameters of sodium, potassium, carbon-dioxide (total), chloride, glucose and urea
    End point description
    Blood samples will be collected for the analysis of clinical chemistry parameters including; sodium, potassium, carbon-dioxide (total), chloride, glucose and urea. Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
    End point type
    Other pre-specified
    End point timeframe
    Days 1, 42 and 59
    End point values
    		 Daprodustat Darbepoetin alfa
    Number of subjects analysed
    2
    3
    Units: Millimoles per Liter
    arithmetic mean (standard deviation)
        Sodium, Day 1, n=2, 3
    140.0 ( 1.41 )
    136.7 ( 0.58 )
        Sodium, Day 42, n=2, 2
    139.5 ( 3.54 )
    135.0 ( 7.07 )
        Sodium, Day 59, n=2, 3
    138.5 ( 0.71 )
    136.0 ( 2.65 )
        Potassium, Day 1, n=2, 3
    4.70 ( 0.141 )
    5.03 ( 0.757 )
        Potassium, Day 42, n=2, 2
    4.55 ( 0.495 )
    5.15 ( 0.495 )
        Potassium, Day 59, n=2, 3
    4.45 ( 0.071 )
    4.77 ( 0.306 )
        Carbon-dioxide (total), Day 1, n=2, 3
    20.5 ( 3.54 )
    19.0 ( 3.46 )
        Carbon-dioxide (total), Day 42, n=2, 2
    22.0 ( 1.41 )
    19.0 ( 0.00 )
        Carbon-dioxide (total), Day 59, n=2, 3
    22.5 ( 2.12 )
    21.0 ( 2.00 )
        Chloride, Day 1, n=2, 3
    108.0 ( 0.00 )
    105.7 ( 5.03 )
        Chloride, Day 42, n=2, 2
    108.0 ( 4.24 )
    104.0 ( 9.90 )
        Chloride, Day 59, n=2, 3
    108.0 ( 2.83 )
    104.7 ( 3.51 )
        Glucose, Day 1, n=2, 3
    7.60 ( 3.111 )
    6.40 ( 4.424 )
        Glucose, Day 42, n=2, 2
    6.95 ( 2.333 )
    12.50 ( 12.162 )
        Glucose, Day 59, n=2, 3
    7.45 ( 4.172 )
    10.10 ( 7.066 )
        Urea, Day 1, n=2, 3
    18.00 ( 2.828 )
    16.67 ( 5.508 )
        Urea, Day 42, n=2, 2
    16.75 ( 2.475 )
    21.00 ( 0.707 )
        Urea, Day 59, n=2, 3
    16.50 ( 0.707 )
    19.33 ( 5.795 )
    No statistical analyses for this end point

    Other pre-specified: Change from Baseline in clinical chemistry parameter: sodium, potassium, carbon-dioxide (total), chloride, glucose and urea

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    End point title
    		 Change from Baseline in clinical chemistry parameter: sodium, potassium, carbon-dioxide (total), chloride, glucose and urea
    End point description
    Blood samples will be collected for the analysis of clinical chemistry parameters including; sodium, potassium, carbon-dioxide (total), chloride, glucose and urea. Baseline value (Day 1) is the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value. Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
    End point type
    Other pre-specified
    End point timeframe
    Baseline (Day 1) and at Days 42 and 59
    End point values
    		 Daprodustat Darbepoetin alfa
    Number of subjects analysed
    2
    3
    Units: Millimoles per Liter
    arithmetic mean (standard deviation)
        Sodium, Day 42, n=2, 2
    -0.5 ( 4.95 )
    -1.5 ( 6.36 )
        Sodium, Day 59, n=2, 3
    -1.5 ( 2.12 )
    -0.7 ( 2.31 )
        Potassium, Day 42, n=2, 2
    -0.15 ( 0.354 )
    -0.05 ( 0.495 )
        Potassium, Day 59, n=2, 3
    -0.25 ( 0.071 )
    -0.27 ( 0.503 )
        Carbon-dioxide (total), Day 42, n=2, 2
    1.5 ( 4.95 )
    1.0 ( 4.24 )
        Carbon-dioxide (total), Day 59, n=2, 3
    2.0 ( 1.41 )
    2.0 ( 2.00 )
        Chloride, Day 42, n=2, 2
    0.0 ( 4.24 )
    -2.0 ( 2.83 )
        Chloride, Day 59, n=2, 3
    0.0 ( 2.83 )
    1.73 ( 1.73 )
        Glucose, Day 42, n=2, 2
    -0.65 ( 0.778 )
    4.25 ( 7.849 )
        Glucose, Day 59, n=2, 3
    -0.15 ( 1.061 )
    3.70 ( 3.477 )
        Urea, Day 42, n=2, 2
    -1.25 ( 5.303 )
    3.00 ( 7.778 )
        Urea, Day 59, n=2, 3
    -1.50 ( 3.536 )
    2.67 ( 2.754 )
    No statistical analyses for this end point

    Other pre-specified: Absolute values of clinical chemistry parameters of creatinine

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    End point title
    		 Absolute values of clinical chemistry parameters of creatinine
    End point description
    Blood samples will be collected for the analysis of clinical chemistry parameters including; creatinine. Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
    End point type
    Other pre-specified
    End point timeframe
    Days 1, 42 and 59
    End point values
    		 Daprodustat Darbepoetin alfa
    Number of subjects analysed
    2
    3
    Units: Micromoles per Liter
    arithmetic mean (standard deviation)
        Creatinine, Day 1, n=2, 3
    246.65 ( 9.970 )
    225.40 ( 74.164 )
        Creatinine, Day 42, n=2, 2
    249.75 ( 15.627 )
    272.25 ( 88.742 )
        Creatinine, Day 59, n=2, 3
    260.35 ( 8.132 )
    245.17 ( 91.086 )
    No statistical analyses for this end point

    Other pre-specified: Change from Baseline in clinical chemistry parameter: creatinine

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    End point title
    		 Change from Baseline in clinical chemistry parameter: creatinine
    End point description
    Blood samples will be collected for the analysis of clinical chemistry parameters including; creatinine. Baseline value (Day 1) is the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value. Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
    End point type
    Other pre-specified
    End point timeframe
    Baseline (Day 1) and at Days 42 and 59
    End point values
    		 Daprodustat Darbepoetin alfa
    Number of subjects analysed
    2
    3
    Units: Micromoles per Liter
    arithmetic mean (standard deviation)
        Creatinine, Day 42, n=2, 2
    3.10 ( 5.657 )
    36.70 ( 13.152 )
        Creatinine, Day 59, n=2, 3
    13.70 ( 18.102 )
    19.77 ( 33.416 )
    No statistical analyses for this end point

    Other pre-specified: Absolute values of clinical chemistry parameters of bilirubin (direct/indirect and total)

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    End point title
    		 Absolute values of clinical chemistry parameters of bilirubin (direct/indirect and total)
    End point description
    Blood samples will be collected for the analysis of clinical chemistry parameters including; bilirubin (direct/indirect and total). Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles). 99999 indicates standard deviation could not be calculated as a single participant was analyzed.
    End point type
    Other pre-specified
    End point timeframe
    Days 1, 14, 28, 42 and 59
    End point values
    		 Daprodustat Darbepoetin alfa
    Number of subjects analysed
    2
    3
    Units: Micromoles per Liter
    arithmetic mean (standard deviation)
        Bilirubin total, Day 1, n=2, 3
    5.0 ( 1.41 )
    6.0 ( 0.00 )
        Bilirubin total, Day 14, n=2, 3
    5.0 ( 1.41 )
    7.3 ( 1.15 )
        Bilirubin total, Day 28, n=2, 3
    6.0 ( 0.00 )
    6.0 ( 0.00 )
        Bilirubin total, Day 42, n=2, 2
    6.0 ( 0.00 )
    9.0 ( 4.24 )
        Bilirubin total, Day 59, n=2, 3
    5.0 ( 1.41 )
    6.7 ( 1.15 )
        Direct Bilirubin, Day 1, n=2, 2
    1.0 ( 1.41 )
    2.0 ( 0.00 )
        Direct Bilirubin, Day 14, n=2, 2
    1.0 ( 1.41 )
    2.0 ( 0.00 )
        Direct Bilirubin, Day 28, n=2, 2
    1.0 ( 1.41 )
    2.0 ( 0.00 )
        Direct Bilirubin, Day 42, n=2, 1
    2.0 ( 0.00 )
    2.0 ( 99999 )
        Direct Bilirubin, Day 59, n=2, 2
    2.0 ( 0.00 )
    2.0 ( 0.00 )
        Indirect Bilirubin, Day 1, n=2, 2
    4.0 ( 0.00 )
    4.0 ( 0.00 )
        Indirect Bilirubin, Day 14, n=2, 2
    4.0 ( 0.00 )
    5.0 ( 1.41 )
        Indirect Bilirubin, Day 28, n=2, 2
    5.0 ( 1.41 )
    4.0 ( 0.00 )
        Indirect Bilirubin, Day 42, n=2, 1
    4.0 ( 0.00 )
    10.0 ( 99999 )
        Indirect Bilirubin, Day 59, n=2, 2
    3.0 ( 1.41 )
    5.0 ( 1.41 )
    No statistical analyses for this end point

    Other pre-specified: Change from Baseline in clinical chemistry parameter: bilirubin (direct/indirect and total)

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    End point title
    		 Change from Baseline in clinical chemistry parameter: bilirubin (direct/indirect and total)
    End point description
    Blood samples will be collected for the analysis of clinical chemistry parameters including; creatinine and bilirubin (direct/indirect and total). Baseline value (Day 1) is the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value. Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles). 99999 indicates standard deviation could not be calculated as a single participant was analyzed.
    End point type
    Other pre-specified
    End point timeframe
    Baseline (Day 1) and at Days 14, 28, 42 and 59
    End point values
    		 Daprodustat Darbepoetin alfa
    Number of subjects analysed
    2
    3
    Units: Micromoles per Liter
    arithmetic mean (standard deviation)
        Bilirubin total, Day 14, n=2, 3
    0.0 ( 0.00 )
    1.3 ( 1.15 )
        Bilirubin total, Day 28, n=2, 3
    1.0 ( 1.41 )
    0.0 ( 0.00 )
        Bilirubin total, Day 42, n=2, 2
    1.0 ( 1.41 )
    3.0 ( 4.24 )
        Bilirubin total, Day 59, n=2, 3
    0.0 ( 0.00 )
    0.7 ( 1.15 )
        Direct Bilirubin, Day 14, n=2, 2
    0.0 ( 0.00 )
    0.0 ( 0.00 )
        Direct Bilirubin, Day 28, n=2, 2
    0.0 ( 0.00 )
    0.0 ( 0.00 )
        Direct Bilirubin, Day 42, n=2, 1
    1.0 ( 1.41 )
    0.0 ( 99999 )
        Direct Bilirubin, Day 59, n=2, 2
    1.0 ( 1.41 )
    0.0 ( 0.00 )
        Indirect Bilirubin, Day 14, n=2, 2
    0.0 ( 0.00 )
    1.0 ( 1.41 )
        Indirect Bilirubin, Day 28, n=2, 2
    1.0 ( 1.41 )
    0.0 ( 0.00 )
        Indirect Bilirubin, Day 42, n=2, 1
    0.0 ( 0.00 )
    6.0 ( 99999 )
        Indirect Bilirubin, Day 59, n=2, 2
    -1.0 ( 1.41 )
    1.0 ( 1.41 )
    No statistical analyses for this end point

    Other pre-specified: Absolute values of clinical chemistry parameters of Alanine transaminase (ALT), Alkaline Phosphatase (ALP) and Aspartate transaminase (AST)

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    End point title
    		 Absolute values of clinical chemistry parameters of Alanine transaminase (ALT), Alkaline Phosphatase (ALP) and Aspartate transaminase (AST)
    End point description
    Blood samples will be collected for the analysis of clinical chemistry parameters including; ALT, ALP and AST. Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
    End point type
    Other pre-specified
    End point timeframe
    Days 1, 14, 28, 42 and 59
    End point values
    		 Daprodustat Darbepoetin alfa
    Number of subjects analysed
    2
    3
    Units: International units per Liter
    arithmetic mean (standard deviation)
        ALT, Day 1, n=2, 3
    21.0 ( 4.24 )
    26.7 ( 7.02 )
        ALT, Day 14, n=2, 3
    15.0 ( 4.24 )
    20.3 ( 6.81 )
        ALT, Day 28, n=2, 3
    15.5 ( 4.95 )
    18.3 ( 8.08 )
        ALT, Day 42, n=2, 2
    16.0 ( 4.24 )
    22.0 ( 9.90 )
        ALT, Day 59, n=2, 3
    20.5 ( 10.61 )
    23.3 ( 8.08 )
        ALP, Day 1, n=2, 3
    113.5 ( 61.52 )
    95.0 ( 42.44 )
        ALP, Day 14, n=2, 3
    97.0 ( 42.43 )
    91.0 ( 33.87 )
        ALP, Day 28, n=2, 3
    99.5 ( 45.96 )
    91.7 ( 38.40 )
        ALP, Day 42, n=2, 2
    99.0 ( 39.60 )
    100.5 ( 37.48 )
        ALP, Day 59, n=2, 3
    108.5 ( 55.86 )
    90.3 ( 29.26 )
        AST, Day 1, n=2, 3
    19.5 ( 7.78 )
    21.7 ( 1.53 )
        AST, Day 14, n=2, 3
    16.5 ( 7.78 )
    18.3 ( 3.51 )
        AST, Day 28, n=2, 3
    18.0 ( 9.90 )
    18.7 ( 7.09 )
        AST, Day 42, n=2, 2
    17.5 ( 10.61 )
    16.5 ( 4.95 )
        AST, Day 59, n=2, 3
    20.5 ( 10.61 )
    19.3 ( 6.03 )
    No statistical analyses for this end point

    Other pre-specified: Change from Baseline in clinical chemistry parameter: ALT, ALP and AST

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    End point title
    		 Change from Baseline in clinical chemistry parameter: ALT, ALP and AST
    End point description
    Blood samples will be collected for the analysis of clinical chemistry parameters including; ALT, ALP and AST. Baseline value (Day 1) is the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value. Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
    End point type
    Other pre-specified
    End point timeframe
    Baseline (Day 1) and at Days 14, 28, 42 and 59
    End point values
    		 Daprodustat Darbepoetin alfa
    Number of subjects analysed
    2
    3
    Units: International units per Liter
    arithmetic mean (standard deviation)
        ALT, Day 14, n=2, 3
    -6.0 ( 0.00 )
    -6.3 ( 1.53 )
        ALT, Day 28, n=2, 3
    -5.5 ( 0.71 )
    -8.3 ( 1.15 )
        ALT, Day 42, n=2, 2
    -5.0 ( 0.00 )
    -5.0 ( 0.00 )
        ALT, Day 59, n=2, 3
    -0.5 ( 6.36 )
    -3.3 ( 4.62 )
        ALP, Day 14, n=2, 3
    -16.5 ( 19.09 )
    -4.0 ( 12.12 )
        ALP, Day 28, n=2, 3
    -14.0 ( 15.56 )
    -3.3 ( 4.04 )
        ALP, Day 42, n=2, 2
    -14.5 ( 21.92 )
    -6.5 ( 14.85 )
        ALP, Day 59, n=2, 3
    -5.0 ( 5.66 )
    -4.7 ( 13.61 )
        AST, Day 14, n=2, 3
    -3.0 ( 0.00 )
    -3.3 ( 2.08 )
        AST, Day 28, n=2, 3
    -1.5 ( 2.12 )
    -3.0 ( 6.00 )
        AST, Day 42, n=2, 2
    -2.0 ( 2.83 )
    -5.0 ( 2.83 )
        AST, Day 59, n=2, 3
    1.0 ( 2.83 )
    -2.3 ( 5.03 )
    No statistical analyses for this end point

    Other pre-specified: Absolute values of clinical chemistry parameters of Albumin

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    End point title
    		 Absolute values of clinical chemistry parameters of Albumin
    End point description
    Blood samples will be collected for the analysis of clinical chemistry parameters including; Albumin. Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
    End point type
    Other pre-specified
    End point timeframe
    Days 1, 14, 28, 42 and 59
    End point values
    		 Daprodustat Darbepoetin alfa
    Number of subjects analysed
    2
    3
    Units: Grams per Liter
    arithmetic mean (standard deviation)
        Day 1, n=2, 3
    37.0 ( 5.66 )
    41.7 ( 2.31 )
        Day 14, n=2, 3
    36.5 ( 2.12 )
    40.7 ( 3.06 )
        Day 28, n=2, 3
    35.5 ( 3.54 )
    39.3 ( 3.21 )
        Day 42, n=2, 2
    35.5 ( 3.54 )
    38.5 ( 0.71 )
        Day 59, n=2, 3
    36.5 ( 6.36 )
    40.3 ( 1.53 )
    No statistical analyses for this end point

    Other pre-specified: Change from Baseline in clinical chemistry parameter: Albumin

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    End point title
    		 Change from Baseline in clinical chemistry parameter: Albumin
    End point description
    Blood samples will be collected for the analysis of clinical chemistry parameters including; Albumin. Baseline value (Day 1) is the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value. Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
    End point type
    Other pre-specified
    End point timeframe
    Baseline (Day 1) and at Days 14, 28, 42 and 59
    End point values
    		 Daprodustat Darbepoetin alfa
    Number of subjects analysed
    2
    3
    Units: Grams per Liter
    arithmetic mean (standard deviation)
        Day 14, n=2, 3
    -0.05 ( 0.354 )
    -0.10 ( 0.200 )
        Day 28, n=2, 3
    -0.15 ( 0.212 )
    -0.23 ( 0.321 )
        Day 42, n=2, 2
    -0.15 ( 0.212 )
    -0.25 ( 0.354 )
        Day 59, n=2, 3
    -0.05 ( 0.071 )
    -0.13 ( 0.153 )
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Non-SAEs and SAEs were collected from the start of the treatment and Up to 59 days
    Adverse event reporting additional description
    Non-SAEs and SAEs were collected in the Safety Population which comprised of participants who received at least one dose of study treatment.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    22.0
    Reporting groups
    Reporting group title
    Darbepoetin alfa
    Reporting group description
    		 Participants were randomized to receive darbepoetin alfa solution for injection, administered as a single subcutaneous injection, once every two weeks (Days 1, 14 and 28).

    Reporting group title
    Daprodustat
    Reporting group description
    		 Participants were randomized to receive 2 milligram (mg) daprodustat tablets once daily via oral route for a period of 41 days.

    Serious adverse events
    		 Darbepoetin alfa Daprodustat
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 2 (0.00%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 Darbepoetin alfa Daprodustat
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 2 (0.00%)
    Gastrointestinal disorders
    Faeces soft
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 2 (0.00%)
         occurrences all number
    1
    0
    Abdominal pain upper
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 2 (0.00%)
         occurrences all number
    1
    0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 2 (0.00%)
         occurrences all number
    1
    0
    Joint swelling
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 2 (0.00%)
         occurrences all number
    1
    0
    Metabolism and nutrition disorders
    Gout
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 2 (0.00%)
         occurrences all number
    1
    0
    Bilateral foot discomfort secondary to Gout
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 2 (0.00%)
         occurrences all number
    1
    0
    Swollen right foot secondary to Gout
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 2 (0.00%)
         occurrences all number
    1
    0

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    29 Jan 2018
    Amendment 01: The study team was required per regulatory agencies to change the protocol to include a serum pregnancy testing at screening. During the amendment process, minor updates were made for study optimization.

    Interruptions (globally)
    Were there any global interruptions to the trial? Yes
    Date
    Interruption
    Restart date
    29 May 2019
    Study pause due to significant protocol amendment
    -

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    Amendment 02: 07-AUG-2019: Study restarted but no participants recruited prior to termination date. Thus not reported due to limitations in disclosure form.
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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