Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   44334   clinical trials with a EudraCT protocol, of which   7366   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    A Multi-Center, Double-Blind, Randomized Study Evaluating De Novo Weekly and Once Every Two Week Darbepoetin Alfa Dosing for the Correction of Anemia in Pediatric Subjects with Chronic Kidney Disease Receiving and Not Receiving Dialysis

    Summary
    EudraCT number
    		 2008-003418-88
    Trial protocol
    		 SK   LV   BE   LT   GB   Outside EU/EEA  
    Global end of trial date
    03 Mar 2014

    Results information
    Results version number
    		 v1(current)
    This version publication date
    20 Jun 2016
    First version publication date
    31 Jul 2015
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    20050256
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT00436748
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Amgen, Inc.
    Sponsor organisation address
    One Amgen Center Drive, Thousand Oaks, CA, United States, 91320
    Public contact
    IHQ Medical Info-Clinical Trials, Amgen (EUROPE) GmbH, MedInfoInternational@amgen.com
    Scientific contact
    IHQ Medical Info-Clinical Trials, Amgen (EUROPE) GmbH, MedInfoInternational@amgen.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    Yes
    EMA paediatric investigation plan number(s)
    		 EMEA-000329-PIP02-09
    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?
    Yes
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    03 Mar 2014
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    03 Mar 2014
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    The primary objectives of this study are the following: 1. To test if the proportion of participants achieving a hemoglobin value greater than or equal to 10.0 g/dL at any time point after the first dose during the study is greater than 0.8 when administered de novo darbepoetin alfa once a week (QW) for treatment of anemia in pediatric patients with chronic kidney disease receiving and not receiving dialysis, and 2. To test if the proportion of participants achieving a hemoglobin value greater than or equal to 10.0 g/dL at any time point after the first dose during the study is greater than 0.8 when administered de novo darbepoetin alfa every 2 weeks (Q2W) for treatment of anemia in pediatric patients with chronic kidney disease receiving and not receiving dialysis.
    Protection of trial subjects
    This study was conducted in accordance with International Conference on Harmonisation (ICH) Good Clinical Practice (GCP) regulations/guidelines and applicable country regulations. Assent from the child, except if the child was very young, and consent from the parents or legal guardian were obtained as defined by local law for all subjects by the investigator or designee after adequate explanation of the aims, methods, anticipated benefits, and potential hazards of the study and before any study-specific procedures were performed or investigational product was administered. The study protocol, amendments, and the informed consent form (ICF) were reviewed by the Institutional Review Boards (IRBs) and Independent Ethics Committees (IECs). No subjects were recruited into the study and no investigational product (IP) was shipped until the IRB/IEC gave written approval of the protocol and ICF and Amgen received copies of these approvals.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    01 Sep 2008
    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
    Latvia: 1
    Country: Number of subjects enrolled
    Lithuania: 5
    Country: Number of subjects enrolled
    Mexico: 5
    Country: Number of subjects enrolled
    Poland: 1
    Country: Number of subjects enrolled
    Russian Federation: 16
    Country: Number of subjects enrolled
    Slovakia: 8
    Country: Number of subjects enrolled
    United Kingdom: 1
    Country: Number of subjects enrolled
    United States: 79
    Worldwide total number of subjects
    116
    EEA total number of subjects
    16
    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)
    41
    Adolescents (12-17 years)
    73
    Adults (18-64 years)
    2
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 This trial enrolled pediatric patients with chronic kidney disease (CKD) who were anemic and not treated with an erythropoiesis-stimulating agent (ESA). The study was conducted at 43 centers in the US, Europe and Mexico. The first participant was enrolled on 16 September 2008 and the last participant was enrolled on 02 December 2013.

    Pre-assignment
    Screening details
    		 A total of 189 participants were screened, 116 participants were enrolled, and 73 screen failed. The primary reasons for screen failure were hemoglobin concentration > 10 g/dL or transferrin saturation < 20%. Randomization was stratified by age and dialysis status.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Darbepoetin Alfa QW
    Arm description
    		 Participants received darbepoetin alfa once a week (QW) for 24 weeks. The initial dose was 0.45 μg/kg; thereafter, active doses were administered to achieve and then maintain hemoglobin levels within a target range of 10.0 to 12.0 g/dL. Participants not on dialysis or who were receiving peritoneal dialysis were administered darbepoetin alfa subcutaneously; participants receiving hemodialysis were administered darbepoetin alfa intravenously.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Darbepoetin Alfa
    Investigational medicinal product code
    Other name
    Aranesp®
    Pharmaceutical forms
    Solution for injection/infusion in pre-filled syringe
    Routes of administration
    Intravenous use, Subcutaneous use
    Dosage and administration details
    Subjects not receiving dialysis and subjects receiving peritoneal dialysis were administered darbepoetin alfa subcutaneously; subjects receiving hemodialysis were administered darbepoetin alfa intravenously.

    Arm title
    		 Darbepoetin Alfa Q2W
    Arm description
    		 Participants received darbepoetin alfa every 2 weeks (Q2W) and a placebo every other 2 weeks to maintain the blind for 24 weeks. The initial dose was 0.75 μg/kg; thereafter, active doses were administered to achieve and then maintain hemoglobin levels within a target range of 10.0 to 12.0 g/dL. Participants not on dialysis or who were receiving peritoneal dialysis were administered darbepoetin alfa subcutaneously; participants receiving hemodialysis were administered darbepoetin alfa intravenously.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Darbepoetin Alfa
    Investigational medicinal product code
    Other name
    Aranesp®
    Pharmaceutical forms
    Solution for injection/infusion in pre-filled syringe
    Routes of administration
    Intravenous use, Subcutaneous use
    Dosage and administration details
    Subjects not receiving dialysis and subjects receiving peritoneal dialysis were administered darbepoetin alfa subcutaneously; subjects receiving hemodialysis were administered darbepoetin alfa intravenously.

    Number of subjects in period 1
    		Darbepoetin Alfa QW Darbepoetin Alfa Q2W
    Started
    59
    57
    Received Treatment
    58
    56
    Completed
    48
    45
    Not completed
    11
    12
         Ineligibility Determined
    1
    1
         Adverse event, non-fatal
    -
    2
         Other
    3
    -
         Administrative Decision
    1
    -
         Lost to follow-up
    -
    1
         Protocol-specified Criteria
    5
    4
         Consent Withdrawn
    1
    4

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Darbepoetin Alfa QW
    Reporting group description
    		 Participants received darbepoetin alfa once a week (QW) for 24 weeks. The initial dose was 0.45 μg/kg; thereafter, active doses were administered to achieve and then maintain hemoglobin levels within a target range of 10.0 to 12.0 g/dL. Participants not on dialysis or who were receiving peritoneal dialysis were administered darbepoetin alfa subcutaneously; participants receiving hemodialysis were administered darbepoetin alfa intravenously.

    Reporting group title
    Darbepoetin Alfa Q2W
    Reporting group description
    		 Participants received darbepoetin alfa every 2 weeks (Q2W) and a placebo every other 2 weeks to maintain the blind for 24 weeks. The initial dose was 0.75 μg/kg; thereafter, active doses were administered to achieve and then maintain hemoglobin levels within a target range of 10.0 to 12.0 g/dL. Participants not on dialysis or who were receiving peritoneal dialysis were administered darbepoetin alfa subcutaneously; participants receiving hemodialysis were administered darbepoetin alfa intravenously.

    Reporting group values
    		 Darbepoetin Alfa QW Darbepoetin Alfa Q2W Total
    Number of subjects
    		 59 57 116
    Age, Customized
    Units: participants
        1 to < 6 years
    		 2 1 3
        6 to < 12 years
    		 19 19 38
        12 to 18 years
    		 38 37 75
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    		 12.7 ( 3.6 ) 12.7 ( 3.7 ) -
    Gender, Male/Female
    Units: participants
        Female
    		 23 23 46
        Male
    		 36 34 70
    Race/Ethnicity, Customized
    Units: Subjects
        White or Caucasian
    		 31 31 62
        Black or African American
    		 4 5 9
        Hispanic or Latino
    		 23 20 43
        Other
    		 1 1 2
    Dialysis Status
    Units: Subjects
        Not receiving dialysis
    		 33 34 67
        Receiving hemodialysis
    		 15 14 29
        Receiving peritoneal dialysis
    		 11 9 20
    Hemoglobin Concentration
    Units: g/dL
        arithmetic mean (standard deviation)
    		 8.59 ( 0.84 ) 8.73 ( 0.84 ) -

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Darbepoetin Alfa QW
    Reporting group description
    		 Participants received darbepoetin alfa once a week (QW) for 24 weeks. The initial dose was 0.45 μg/kg; thereafter, active doses were administered to achieve and then maintain hemoglobin levels within a target range of 10.0 to 12.0 g/dL. Participants not on dialysis or who were receiving peritoneal dialysis were administered darbepoetin alfa subcutaneously; participants receiving hemodialysis were administered darbepoetin alfa intravenously.

    Reporting group title
    Darbepoetin Alfa Q2W
    Reporting group description
    		 Participants received darbepoetin alfa every 2 weeks (Q2W) and a placebo every other 2 weeks to maintain the blind for 24 weeks. The initial dose was 0.75 μg/kg; thereafter, active doses were administered to achieve and then maintain hemoglobin levels within a target range of 10.0 to 12.0 g/dL. Participants not on dialysis or who were receiving peritoneal dialysis were administered darbepoetin alfa subcutaneously; participants receiving hemodialysis were administered darbepoetin alfa intravenously.

    Primary: Proportion of Participants Achieving Hemoglobin ≥ 10.0 g/dL

    		 Close Top of page
    End point title
    		 Proportion of Participants Achieving Hemoglobin ≥ 10.0 g/dL [1]
    End point description
    The proportion of participants achieving hemoglobin ≥ 10.0 g/dL (the correction proportion) was calculated as the number of participants achieving a hemoglobin ≥ 10.0 g/dL at any time point during the study when administered de novo darbepoetin alfa without receiving any red blood cell transfusion after randomization and within 90 days before the achievement, divided by the number of participants in the efficacy analysis set. Analysis was performed using the efficacy analysis set, which includes all participants who received ≥ 1 dose of investigational product.
    End point type
    Primary
    End point timeframe
    24 weeks
    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: No comparisons between groups were planned or conducted for the primary efficacy endpoint. The null hypotheses were tested separately in subjects receiving darbepoetin alfa QW and Q2W, however, the EudraCT system does not accept statistical analyses for single arms.
    End point values
    		 Darbepoetin Alfa QW Darbepoetin Alfa Q2W
    Number of subjects analysed
    58
    56
    Units: proportion of participants
        number (confidence interval 95%)
    0.983 (0.908 to 1)
    0.839 (0.717 to 0.924)
    No statistical analyses for this end point

    Secondary: Time to First Hemoglobin Value ≥ 10.0 g/dL

    		 Close Top of page
    End point title
    		 Time to First Hemoglobin Value ≥ 10.0 g/dL
    End point description
    The time from study Day 1 to the day a participant first achieved hemoglobin ≥ 10.0 g/dL for participants who achieved hemoglobin ≥ 10.0 g/dL.
    End point type
    Secondary
    End point timeframe
    24 weeks
    End point values
    		 Darbepoetin Alfa QW Darbepoetin Alfa Q2W
    Number of subjects analysed
    57 [2]
    47 [3]
    Units: days
        median (inter-quartile range (Q1-Q3))
    24 (15 to 50)
    22 (14 to 41)
    Notes
    [2] - Efficacy analysis set responders
    [3] - Efficacy analysis set responders
    No statistical analyses for this end point

    Secondary: Hemoglobin Concentration Over Time

    		 Close Top of page
    End point title
    		 Hemoglobin Concentration Over Time
    End point description
    End point type
    Secondary
    End point timeframe
    Baseline and Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24 and 25.
    End point values
    		 Darbepoetin Alfa QW Darbepoetin Alfa Q2W
    Number of subjects analysed
    58
    56
    Units: g/dL
    arithmetic mean (standard deviation)
        Baseline (n=58, 56)
    8.59 ( 0.84 )
    8.73 ( 0.84 )
        Week 1 (n=53, 50)
    8.64 ( 0.9 )
    8.65 ( 0.95 )
        Week 2 (n=52, 52)
    8.74 ( 1.09 )
    8.96 ( 1.2 )
        Week 3 (n=51, 55)
    9.28 ( 1.27 )
    9.09 ( 1.27 )
        Week 4 (n=53, 53)
    9.79 ( 1.3 )
    9.55 ( 1.23 )
        Week 5 (n=53, 52)
    10.18 ( 1.29 )
    9.87 ( 1.32 )
        Week 6 (n=54, 50)
    10.54 ( 1.43 )
    10.19 ( 1.33 )
        Week 7 (n=52, 48)
    10.96 ( 1.53 )
    10.17 ( 1.25 )
        Week 8 (n=53, 51)
    11.05 ( 1.37 )
    10.47 ( 1.21 )
        Week 9 (n=50, 51)
    11.03 ( 1.48 )
    10.6 ( 1.34 )
        Week 10 (n=54, 51)
    11.32 ( 1.33 )
    10.6 ( 1.29 )
        Week 11 (n=51, 48)
    11.34 ( 1.33 )
    10.73 ( 1.22 )
        Week 12 (n=51, 48)
    11.45 ( 1.25 )
    10.87 ( 1.38 )
        Week 13 (n=50, 47)
    11.68 ( 1.19 )
    10.82 ( 1.33 )
        Week 14 (n=52, 50)
    11.27 ( 1.28 )
    10.92 ( 1.31 )
        Week 15 (n=49, 50)
    11.25 ( 1.13 )
    11 ( 1.23 )
        Week 16 (n=48, 47)
    11.36 ( 1.19 )
    10.86 ( 1.21 )
        Week 17 (n=48, 48)
    11.21 ( 1.23 )
    11.05 ( 1 )
        Week 18 (n=49, 46)
    11.14 ( 1.2 )
    10.91 ( 1.09 )
        Week 19 (n=48, 46)
    11.06 ( 0.91 )
    10.91 ( 1.09 )
        Week 20 (n=48, 45)
    11.09 ( 1.03 )
    10.76 ( 1 )
        Week 21 (n=48, 46)
    11.2 ( 1.04 )
    10.64 ( 0.99 )
        Week 22 (n=48, 45)
    11 ( 1.19 )
    10.58 ( 1.04 )
        Week 23 (n=48, 44)
    10.93 ( 1.1 )
    10.5 ( 1.05 )
        Week 24 (n=45, 46)
    10.93 ( 1.16 )
    10.43 ( 0.97 )
        Week 25 (n= 32, 31)
    11.13 ( 1.1 )
    10.65 ( 0.75 )
    No statistical analyses for this end point

    Secondary: Weight-adjusted Darbepoetin Alfa Dose at Time of Achieving First Hemoglobin ≥ 10.0 g/dL

    		 Close Top of page
    End point title
    		 Weight-adjusted Darbepoetin Alfa Dose at Time of Achieving First Hemoglobin ≥ 10.0 g/dL
    End point description
    The darbepoetin alfa dose at the time a participant achieved a first hemoglobin level ≥ 10.0 g/dL, divided by the participant's weight measured at the closest study week prior to the dosing, post dialysis.
    End point type
    Secondary
    End point timeframe
    24 weeks
    End point values
    		 Darbepoetin Alfa QW Darbepoetin Alfa Q2W
    Number of subjects analysed
    54 [4]
    44 [5]
    Units: μg/kg
        arithmetic mean (standard deviation)
    0.48 ( 0.24 )
    0.76 ( 0.21 )
    Notes
    [4] - Efficacy analysis set responders for whom dosing data were available.
    [5] - Efficacy analysis set responders for whom dosing data were available.
    No statistical analyses for this end point

    Secondary: Darbepoetin Alfa Weight-Adjusted Dose Over Time

    		 Close Top of page
    End point title
    		 Darbepoetin Alfa Weight-Adjusted Dose Over Time
    End point description
    Arithmetic means are provided; Withheld doses are counted as 0 μg. Numbers > 0 on non-darbepoetin alfa dosing weeks for the Q2W group reflect participants who did not receive the assigned placebo dose (eg, dose withheld per investigator decision based on hemoglobin value or missed visit). "9999" indicates not applicable since subjects received dosing every 2 weeks. "99999" indicates values that could not be calculated since sample size = 1.
    End point type
    Secondary
    End point timeframe
    Day 1 (initial dose) and Weeks 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24 and 25.
    End point values
    		 Darbepoetin Alfa QW Darbepoetin Alfa Q2W
    Number of subjects analysed
    58
    56
    Units: μg/kg
    arithmetic mean (standard deviation)
        Initial Dose (n=58, 56)
    0.45 ( 0.07 )
    0.73 ( 0.13 )
        Week 2 (n=55, 0)
    0.45 ( 0.07 )
    9999 ( 9999 )
        Week 3 (n=55, 52)
    0.44 ( 0.07 )
    0.72 ( 0.11 )
        Week 4 (n=54, 0)
    0.4 ( 0.11 )
    9999 ( 9999 )
        Week 5 (n=54, 51)
    0.43 ( 0.26 )
    0.72 ( 0.25 )
        Week 6 (n=54, 0)
    0.42 ( 0.29 )
    9999 ( 9999 )
        Week 7 (n=54, 51)
    0.38 ( 0.25 )
    0.7 ( 0.28 )
        Week 8 (n=53, 1)
    0.34 ( 0.24 )
    0 ( 99999 )
        Week 9 (n=52, 52)
    0.32 ( 0.23 )
    0.64 ( 0.26 )
        Week 10 (n=55, 3)
    0.33 ( 0.26 )
    0 ( 0 )
        Week 11 (n=54, 50)
    0.32 ( 0.28 )
    0.61 ( 0.35 )
        Week 12 (n=54, 2)
    0.26 ( 0.28 )
    0 ( 0 )
        Week 13 (n=54, 50)
    0.24 ( 0.28 )
    0.56 ( 0.35 )
        Week 14 (n=53, 4)
    0.21 ( 0.27 )
    0 ( 0 )
        Week 15 (n=52, 48)
    0.31 ( 0.33 )
    0.53 ( 0.36 )
        Week 16 (n=50, 5)
    0.35 ( 0.44 )
    0 ( 0 )
        Week 17 (n=51, 47)
    0.29 ( 0.34 )
    0.61 ( 0.97 )
        Week 18 (n=50, 3)
    0.32 ( 0.4 )
    0 ( 0 )
        Week 19 (n=50, 46)
    0.31 ( 0.33 )
    0.45 ( 0.3 )
        Week 20 (n=48, 4)
    0.35 ( 0.34 )
    0 ( 0 )
        Week 21 (n=48, 46)
    0.38 ( 0.63 )
    0.47 ( 0.36 )
        Week 22 (n=48, 3)
    0.38 ( 0.64 )
    0 ( 0 )
        Week 23 (n=47, 44)
    0.39 ( 0.63 )
    0.49 ( 0.4 )
        Week 24 (n=46, 1)
    0.41 ( 0.63 )
    0 ( 99999 )
    No statistical analyses for this end point

    Secondary: Change From Baseline at Week 13 and Week 25 in Parent-reported Pediatric Quality of Life Inventory (PedsQL) Scores

    		 Close Top of page
    End point title
    		 Change From Baseline at Week 13 and Week 25 in Parent-reported Pediatric Quality of Life Inventory (PedsQL) Scores
    End point description
    The PedsQL is a health-related quality of life (HRQOL) questionnaire that can be used to measure quality of life in children ≥ 2 years old. The 23-item PedsQL 4.0 includes physical functioning (8 items), emotional functioning (5 items), social functioning (5 items), and school functioning (5 items). Separate questionnaires for ages 2 to 4 (toddler), 5-7, 8-12, and 13-18 years are used for parent proxy-reporting, which assesses parents’ perceptions of their child’s HRQOL. The instructions ask how much of a problem each item has been during the past 1 month; each item is answered on a 5-point scale: 0 = never a problem; 1 = almost never a problem; 2 = sometimes a problem; 3 = often a problem; 4 = almost always a problem. Scores from the 4 subscales, the total score, and the psychosocial composite score were generated using standard algorithms. Each item’s score in the questionnaire was converted to a 0 to 100 scale (with higher scores indicating better HRQOL).
    End point type
    Secondary
    End point timeframe
    Baseline, Week 13 and Week 25 (or end of study visit if earlier than Week 25)
    End point values
    		 Darbepoetin Alfa QW Darbepoetin Alfa Q2W
    Number of subjects analysed
    45 [6]
    46 [7]
    Units: units on a scale
    arithmetic mean (standard error)
        Week 13 Total Score (n=45, 46)
    4.5 ( 2.19 )
    0.58 ( 2.43 )
        Week 13 Psychosocial composite score (n=45, 46)
    5.12 ( 2.16 )
    -0.41 ( 2.57 )
        Week 13 Physical function score (n=45, 46)
    3.61 ( 3.2 )
    2.31 ( 3.35 )
        Week 13 Emotional function score (n=45, 46)
    1 ( 3 )
    -3.89 ( 2.74 )
        Week 13 Social function score (n=45, 46)
    6.89 ( 3.54 )
    0.76 ( 3.56 )
        Week 13 School function score (n=42, 42)
    7.3 ( 2.47 )
    4.17 ( 3.63 )
        Week 25 Total Score (n=38, 41)
    1.9 ( 2.06 )
    0.65 ( 2.66 )
        Week 25 Psychosocial composite score (n=38, 41)
    2.52 ( 1.83 )
    -1.84 ( 3.13 )
        Week 25 Physical function score (n=38, 41)
    0.66 ( 3.89 )
    5.18 ( 3.59 )
        Week 25 Emotional function score (n=38, 41)
    -0.66 ( 2.61 )
    -3.51 ( 3.16 )
        Week 25 Social function score (n=38, 41)
    5.13 ( 2.64 )
    -2.2 ( 4.1 )
        Week 25 School function score (n=36, 37)
    3.9 ( 2.51 )
    2.03 ( 3.94 )
    Notes
    [6] - Efficacy analysis set with available data
    [7] - Efficacy analysis set with available data
    No statistical analyses for this end point

    Secondary: Change From Baseline at Week 13 and Week 25 in Child Self-reported Pediatric Quality of Life Inventory (PedsQL) Scores

    		 Close Top of page
    End point title
    		 Change From Baseline at Week 13 and Week 25 in Child Self-reported Pediatric Quality of Life Inventory (PedsQL) Scores
    End point description
    The PedsQL child self-reported questionnaire was used in children > 5 years old. The 23-item PedsQL 4.0 includes physical functioning (8 items), emotional functioning (5 items), social functioning (5 items), and school functioning (5 items). Separate questionnaires for ages 5-7, 8-12, and 13-18 years was used for child self-reporting. The instructions asked how much of a problem each item has been during the past 1 month; each item is answered on a 5-point scale for ages 8 to 18 (0 = never a problem; 1 = almost never a problem; 2 = sometimes a problem; 3 = often a problem; 4 = almost always a problem), or simplified to a 3-point scale for ages 5 to 7 (0 = not at all a problem; 2 = sometimes a problem; 4 = a lot of a problem). Scores from the 4 subscales, the total score, and the psychosocial composite score were generated using standard algorithms. Each item’s score in the questionnaire was converted to a 0 to 100 scale (with higher scores indicating better HRQOL).
    End point type
    Secondary
    End point timeframe
    Baseline, Week 13 and Week 25 (or end of study visit if earlier than Week 25)
    End point values
    		 Darbepoetin Alfa QW Darbepoetin Alfa Q2W
    Number of subjects analysed
    46 [8]
    46 [9]
    Units: units on a scale
    arithmetic mean (standard error)
        Week 13 Total Score (n=46, 46)
    2.94 ( 1.7 )
    -1.23 ( 2.04 )
        Week 13 Psychosocial composite score (n=46, 46)
    2.59 ( 1.92 )
    -0.45 ( 2.23 )
        Week 13 Physical function score (n=46, 46)
    3.78 ( 2.43 )
    -2.79 ( 2.59 )
        Week 13 Emotional function score (n=46, 46)
    0.43 ( 2.52 )
    -0.76 ( 2.79 )
        Week 13 Social function score (n=46, 46)
    3.26 ( 2.93 )
    -2.28 ( 3.02 )
        Week 13 School function score (n=45, 43)
    2.89 ( 2.98 )
    2.44 ( 3.83 )
        Week 25 Total Score (n=40, 42)
    5 ( 1.75 )
    2.58 ( 1.78 )
        Week 25 Psychosocial composite score (n=40, 42)
    3.81 ( 1.97 )
    3.53 ( 2.01 )
        Week 25 Physical function score (n=40, 42)
    7.42 ( 2.48 )
    0.74 ( 2.8 )
        Week 25 Emotional function score (n=40, 42)
    -0.25 ( 2.51 )
    3.93 ( 3.1 )
        Week 25 Social function score (n=40, 42)
    7 ( 3.1 )
    2.5 ( 2.67 )
        Week 25 School function score (n=40, 39)
    4.25 ( 3.14 )
    3.85 ( 3.09 )
    Notes
    [8] - Efficacy analysis set aged > 5 years and with available data
    [9] - Efficacy analysis set aged > 5 years and with available data
    No statistical analyses for this end point

    Secondary: Number of Participants with Treatment-emergent Adverse Events

    		 Close Top of page
    End point title
    		 Number of Participants with Treatment-emergent Adverse Events
    End point description
    A serious adverse event (SAE) is defined as an adverse event that meets at least one of the following serious criteria: • is fatal, • is life threatening, • requires in-patient hospitalization or prolongation of existing hospitalization, • results in persistent or significant disability/incapacity, • is a congenital anomaly/birth defect, and/or • other significant medical hazard. The investigator assessed whether the adverse event was related to the investigational product (IP). Events of interest included hypertension, ischemic heart disease, cardiac failure, cerebrovascular disorders, convulsions, embolic and thrombotic events, embolic and thrombotic events: venous, embolic and thrombotic events: arterial, embolic and thrombotic events: vessel type unspecified and mixed arterial and venous, dialysis vascular access thrombosis, antibody-mediated pure red cell aplasia, hypersensitivity, lack of efficacy-effect, and malignancies.
    End point type
    Secondary
    End point timeframe
    25 weeks
    End point values
    		 Darbepoetin Alfa QW Darbepoetin Alfa Q2W
    Number of subjects analysed
    58 [10]
    56 [11]
    Units: participants
    number (not applicable)
        All adverse events
    48
    50
        Serious adverse events
    16
    14
        Leading to discontinuation of IP
    0
    2
        Leading to discontinuation from study
    0
    2
        Fatal adverse events
    0
    0
        Events of interest
    18
    20
        Treatment-related adverse events (TRAE)
    14
    16
        Treatment-related serious adverse events
    1
    2
        TRAE leading to discontinuation of IP
    0
    2
        TRAE leading to discontinuation from study
    0
    2
        Treatment-related fatal adverse events
    0
    0
        Treatment-related events of interest
    6
    9
    Notes
    [10] - Safety analysis set
    [11] - Safety analysis set
    No statistical analyses for this end point

    Secondary: Hemoglobin Serial Rate of Change (ROC) Over Time

    		 Close Top of page
    End point title
    		 Hemoglobin Serial Rate of Change (ROC) Over Time
    End point description
    Calculated using the serial method as the change in hemoglobin from the previous non-missing hemoglobin level divided by number of days in between, and then multiplied by 7.
    End point type
    Secondary
    End point timeframe
    Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24 and 25.
    End point values
    		 Darbepoetin Alfa QW Darbepoetin Alfa Q2W
    Number of subjects analysed
    58 [12]
    56 [13]
    Units: g/dL/week
    median (full range (min-max))
        Week 2 (n=49, 47)
    0.263 (-0.9 to 1.17)
    0.35 (-1.82 to 2.1)
        Week 3 (n=50, 53)
    0.53 (-1 to 1.7)
    0.2 (-1.23 to 1.4)
        Week 4 (n=53, 52)
    0.56 (-0.4 to 2.2)
    0.513 (-1.6 to 3.33)
        Week 5 (n=53, 49)
    0.438 (-2 to 2)
    0.117 (-3.92 to 1.52)
        Week 6 (n=54, 48)
    0.4 (-2.5 to 2.4)
    0.231 (-1.05 to 2.4)
        Week 7 (n=51, 45)
    0.2 (-1.2 to 2.9)
    0.1 (-1.75 to 2.57)
        Week 8 (n=52, 49)
    0.163 (-1.98 to 1.63)
    0.3 (-2.71 to 1.17)
        Week 9 (n=49, 50)
    0.1 (-2.8 to 1.4)
    0.089 (-1.3 to 2.2)
        Week 10 (n=53, 50)
    0.117 (-1.4 to 3.9)
    0 (-2.1 to 1.52)
        Week 11 (n=51, 48)
    0.1 (-2.1 to 1.87)
    0.138 (-1.49 to 1.49)
        Week 12 (n=51, 48)
    0 (-1.4 to 4.4)
    0.2 (-2.2 to 1.1)
        Week 13 (n=50, 47)
    0.128 (-2.8 to 2.7)
    -0.064 (-2.57 to 2.19)
        Week 14 (n=52, 50)
    -0.419 (-1.87 to 2.4)
    0.023 (-1.4 to 1.4)
        Week 15 (n=49, 50)
    0.2 (-1.6 to 2.33)
    0.128 (-2.38 to 1.63)
        Week 16 (n=48, 47)
    0 (-2.1 to 3.27)
    -0.1 (-3.2 to 1.1)
        Week 17 (n=47, 48)
    -0.1 (-2.8 to 2.4)
    0.139 (-1 to 2)
        Week 18 (n=48, 46)
    -0.188 (-2.3 to 1.4)
    0.094 (-2.33 to 1.4)
        Week 19 (n=47, 46)
    0.1 (-1.52 to 1.2)
    -0.1 (-2.22 to 3.9)
        Week 20 (n=47, 44)
    0 (-1.9 to 2.6)
    -0.05 (-3.2 to 1.1)
        Week 21 (n=47, 45)
    0.1 (-1.48 to 2.45)
    -0.14 (-1.2 to 1.4)
        Week 22 (n=48, 44)
    -0.2 (-2.6 to 1.1)
    0 (-1.7 to 1.6)
        Week 23 (n=47, 43)
    -0.1 (-2.8 to 1.75)
    0 (-1.54 to 1.82)
        Week 24 (n=44, 46)
    0.1 (-3.03 to 4.34)
    0.05 (-1.6 to 6.44)
        Week 25 (n=32, 31)
    0.188 (-1.2 to 2.1)
    0 (-1.05 to 1.68)
    Notes
    [12] - Safety analyis set with available data
    [13] - Safety analyis set with available data
    No statistical analyses for this end point

    Secondary: Number of Participants with Hemoglobin > 12.0, > 13.0, and > 14.0 g/dL During the Study

    		 Close Top of page
    End point title
    		 Number of Participants with Hemoglobin > 12.0, > 13.0, and > 14.0 g/dL During the Study
    End point description
    End point type
    Secondary
    End point timeframe
    25 weeks
    End point values
    		 Darbepoetin Alfa QW Darbepoetin Alfa Q2W
    Number of subjects analysed
    58
    56
    Units: participants
    number (not applicable)
        Number of participants with hemoglobin > 12.0 g/dL
    44
    33
        Number of participants with hemoglobin > 13.0 g/dL
    24
    6
        Number of participants with hemoglobin > 14.0 g/dL
    6
    2
    No statistical analyses for this end point

    Secondary: Maximum Increase in Hemoglobin Over Any 2 Week Period

    		 Close Top of page
    End point title
    		 Maximum Increase in Hemoglobin Over Any 2 Week Period
    End point description
    The maximum increase between any 2 non-missing hemoglobin measurements over any 2-week period from Day 1.
    End point type
    Secondary
    End point timeframe
    25 weeks
    End point values
    		 Darbepoetin Alfa QW Darbepoetin Alfa Q2W
    Number of subjects analysed
    58
    56
    Units: g/dL/2 weeks
        arithmetic mean (standard deviation)
    2.06 ( 0.88 )
    1.61 ( 0.76 )
    No statistical analyses for this end point

    Secondary: Change from Baseline in Systolic Blood Pressure Over Time

    		 Close Top of page
    End point title
    		 Change from Baseline in Systolic Blood Pressure Over Time
    End point description
    End point type
    Secondary
    End point timeframe
    Baseline and Weeks 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24 and 25.
    End point values
    		 Darbepoetin Alfa QW Darbepoetin Alfa Q2W
    Number of subjects analysed
    58
    56
    Units: mmHg
    arithmetic mean (standard deviation)
        Week 2 (n=55, 54)
    1.7 ( 11.6 )
    -3.9 ( 11.1 )
        Week 3 (n=55, 56)
    1.1 ( 14.1 )
    0 ( 12.7 )
        Week 4 (n=55, 54)
    1.3 ( 13 )
    1.2 ( 11.5 )
        Week 5 (n=55, 52)
    1.1 ( 13.7 )
    -3 ( 13.7 )
        Week 6 (n=54, 51)
    0.2 ( 14.2 )
    -2.9 ( 12.5 )
        Week 7 (n=54, 52)
    -1 ( 14.2 )
    -3.7 ( 13.4 )
        Week 8 (n=55, 52)
    0.5 ( 16 )
    -2.7 ( 13.8 )
        Week 9 (n=54, 52)
    1 ( 18.3 )
    -3.1 ( 14.5 )
        Week 10 (n=55, 52)
    -0.2 ( 16.6 )
    -3.7 ( 14.6 )
        Week 11 (n=54, 51)
    -2 ( 15.6 )
    -1.8 ( 15.9 )
        Week 12 (n=55, 49)
    -2.4 ( 17.2 )
    -2.8 ( 15.4 )
        Week 13 (n=53, 50)
    0.5 ( 14.8 )
    -2.1 ( 14.2 )
        Week 14 (n=54, 50)
    -2.3 ( 19.5 )
    -1.8 ( 15.8 )
        Week 15 (n=53, 50)
    0.1 ( 17.4 )
    -2.4 ( 13 )
        Week 16 (n=50, 48)
    1.9 ( 16.4 )
    -3.8 ( 16.3 )
        Week 17 (n=51, 47)
    1 ( 17.7 )
    0.1 ( 10.6 )
        Week 18 (n=50, 46)
    0.5 ( 18.5 )
    0 ( 15.5 )
        Week 19 (n=50, 47)
    3.4 ( 16 )
    -2.5 ( 14.2 )
        Week 20 (n=48, 46)
    -0.9 ( 18.3 )
    -4 ( 13 )
        Week 21 (n=49, 46)
    1.9 ( 15.7 )
    -2.2 ( 15 )
        Week 22 (n=48, 46)
    -0.6 ( 18.2 )
    -0.9 ( 15 )
        Week 23 (n=47, 45)
    -0.6 ( 16.5 )
    -1.2 ( 15.7 )
        Week 24 (n=46, 46)
    0 ( 17.8 )
    -2 ( 11.8 )
        Week 25 (n=34, 32)
    -0.5 ( 14.3 )
    -2.3 ( 12.4 )
    No statistical analyses for this end point

    Secondary: Change from Baseline in Diastolic Blood Pressure Over Time

    		 Close Top of page
    End point title
    		 Change from Baseline in Diastolic Blood Pressure Over Time
    End point description
    End point type
    Secondary
    End point timeframe
    Baseline and Weeks 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24 and 25.
    End point values
    		 Darbepoetin Alfa QW Darbepoetin Alfa Q2W
    Number of subjects analysed
    58
    56
    Units: mmHg
    arithmetic mean (standard deviation)
        Week 2 (n=55, 54)
    1.4 ( 9.4 )
    0.8 ( 11.1 )
        Week 3 (n=55, 56)
    2.2 ( 11 )
    3.1 ( 10.8 )
        Week 4 (n=55, 54)
    2.8 ( 11 )
    1.8 ( 12.6 )
        Week 5 (n=55, 52)
    3 ( 12.4 )
    -0.2 ( 11.2 )
        Week 6 (n=54, 51)
    2.6 ( 10.1 )
    -0.1 ( 11.4 )
        Week 7 (n=54, 52)
    1.2 ( 10.4 )
    -1 ( 12.3 )
        Week 8 (n=55, 52)
    3.9 ( 11.9 )
    1.1 ( 15 )
        Week 9 (n=54, 52)
    4.8 ( 14.7 )
    -0.3 ( 12.9 )
        Week 10 (n=55, 52)
    1.5 ( 13.7 )
    0.9 ( 15.9 )
        Week 11 (n=54, 51)
    3.9 ( 11.8 )
    0.9 ( 14.4 )
        Week 12 (n=55, 49)
    1.6 ( 10.4 )
    2.8 ( 13.7 )
        Week 13 (n=54, 50)
    2.7 ( 13.8 )
    2.2 ( 10.6 )
        Week 14 (n=54, 50)
    3.4 ( 14.4 )
    1.7 ( 12 )
        Week 15 (n=53, 50)
    3.7 ( 12.9 )
    1.4 ( 11.7 )
        Week 16 (n=50, 48)
    4.6 ( 13.7 )
    0.7 ( 11.9 )
        Week 17 (n=51, 47)
    4.1 ( 15.6 )
    2.6 ( 10.6 )
        Week 18 (n=50, 46)
    3 ( 16.4 )
    0.4 ( 11.7 )
        Week 19 (n=50, 47)
    3.7 ( 12.9 )
    0.6 ( 12.2 )
        Week 20 (n=48, 46)
    1.7 ( 13.8 )
    2 ( 13.2 )
        Week 21 (n=49, 46)
    2.9 ( 15.1 )
    0.6 ( 12.9 )
        Week 22 (n=48, 46)
    3.2 ( 14.7 )
    0.3 ( 13.9 )
        Week 23 (n=47, 45)
    5 ( 13.8 )
    -2 ( 14 )
        Week 24 (n=46, 46)
    4 ( 13.8 )
    -0.3 ( 12.8 )
        Week 25 (n=34, 32)
    3 ( 13 )
    -1.5 ( 10.7 )
    No statistical analyses for this end point

    Secondary: Number of Participants who Developed Anti-erythropoiesis Antibodies

    		 Close Top of page
    End point title
    		 Number of Participants who Developed Anti-erythropoiesis Antibodies
    End point description
    Participants who were negative for anti-erythropoiesis antibodies at Baseline (pre-dose) and who developed anti-erythropoiesis antibodies during the study. Serum samples were tested using Amgen’s Surface Plasmon Resonance Immunoassay (SPRIA) method.
    End point type
    Secondary
    End point timeframe
    25 weeks
    End point values
    		 Darbepoetin Alfa QW Darbepoetin Alfa Q2W
    Number of subjects analysed
    49 [14]
    49 [15]
    Units: participants
        number (not applicable)
    2
    4
    Notes
    [14] - Safety analysis set with both pre and postdose immunoassay antibody results
    [15] - Safety analysis set with both pre and postdose immunoassay antibody results
    No statistical analyses for this end point

    Secondary: Darbepoetin Alfa Serum Concentrations for Participants Less Than 6 Years of Age

    		 Close Top of page
    End point title
    		 Darbepoetin Alfa Serum Concentrations for Participants Less Than 6 Years of Age
    End point description
    Serum concentrations of darbepoetin alfa were measured by an enzyme-linked immunosorbent assay (ELISA).
    End point type
    Secondary
    End point timeframe
    Weeks 1, 2, and 3 before the investigational product dose and 2 days after the first investigational product dose
    End point values
    		 Darbepoetin Alfa QW Darbepoetin Alfa Q2W
    Number of subjects analysed
    0 [16]
    0 [17]
    Units: ng/mL
        arithmetic mean (standard deviation)
    ( )
    ( )
    Notes
    [16] - Due to the low number of subjects <6 years of age summary concentration analyses were not performed.
    [17] - Due to the low number of subjects <6 years of age summary concentration analyses were not performed.
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    25 weeks
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    16.1
    Reporting groups
    Reporting group title
    Darbepoetin Alfa QW
    Reporting group description
    		 Participants received darbepoetin alfa once a week (QW) for 24 weeks. The initial dose was 0.45 μg/kg; thereafter, active doses were administered to achieve and then maintain hemoglobin levels within a target range of 10.0 to 12.0 g/dL. Participants not on dialysis or who were receiving peritoneal dialysis were administered darbepoetin alfa subcutaneously; participants receiving hemodialysis were administered darbepoetin alfa intravenously.

    Reporting group title
    Darbepoetin Alfa Q2W
    Reporting group description
    		 Participants received darbepoetin alfa every 2 weeks (Q2W) and a placebo every other 2 weeks to maintain the blind for 24 weeks. The initial dose was 0.75 μg/kg; thereafter, active doses were administered to achieve and then maintain hemoglobin levels within a target range of 10.0 to 12.0 g/dL. Participants not on dialysis or who were receiving peritoneal dialysis were administered darbepoetin alfa subcutaneously; participants receiving hemodialysis were administered darbepoetin alfa intravenously.

    Serious adverse events
    		 Darbepoetin Alfa QW Darbepoetin Alfa Q2W
    Total subjects affected by serious adverse events
         subjects affected / exposed
    16 / 58 (27.59%)
    14 / 56 (25.00%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    Vascular disorders
    Hypertension
         subjects affected / exposed
    1 / 58 (1.72%)
    3 / 56 (5.36%)
         occurrences causally related to treatment / all
    0 / 1
    2 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypertensive crisis
         subjects affected / exposed
    1 / 58 (1.72%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypotension
         subjects affected / exposed
    0 / 58 (0.00%)
    2 / 56 (3.57%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Orthostatic hypotension
         subjects affected / exposed
    0 / 58 (0.00%)
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Device failure
         subjects affected / exposed
    1 / 58 (1.72%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Device malfunction
         subjects affected / exposed
    1 / 58 (1.72%)
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Local swelling
         subjects affected / exposed
    1 / 58 (1.72%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Medical device complication
         subjects affected / exposed
    1 / 58 (1.72%)
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oedema
         subjects affected / exposed
    1 / 58 (1.72%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    1 / 58 (1.72%)
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Pulmonary oedema
         subjects affected / exposed
    1 / 58 (1.72%)
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Upper respiratory tract inflammation
         subjects affected / exposed
    0 / 58 (0.00%)
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Arteriovenous fistula site complication
         subjects affected / exposed
    1 / 58 (1.72%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arteriovenous fistula site haematoma
         subjects affected / exposed
    1 / 58 (1.72%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrostomy failure
         subjects affected / exposed
    0 / 58 (0.00%)
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post procedural haemorrhage
         subjects affected / exposed
    1 / 58 (1.72%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Tachycardia
         subjects affected / exposed
    0 / 58 (0.00%)
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Headache
         subjects affected / exposed
    2 / 58 (3.45%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypertensive encephalopathy
         subjects affected / exposed
    1 / 58 (1.72%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    1 / 58 (1.72%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Histiocytosis haematophagic
         subjects affected / exposed
    0 / 58 (0.00%)
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    Tinnitus
         subjects affected / exposed
    0 / 58 (0.00%)
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    2 / 58 (3.45%)
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    1 / 58 (1.72%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Decubitus ulcer
         subjects affected / exposed
    0 / 58 (0.00%)
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Swelling face
         subjects affected / exposed
    1 / 58 (1.72%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Renal failure acute
         subjects affected / exposed
    1 / 58 (1.72%)
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal failure chronic
         subjects affected / exposed
    0 / 58 (0.00%)
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal impairment
         subjects affected / exposed
    2 / 58 (3.45%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vesical fistula
         subjects affected / exposed
    0 / 58 (0.00%)
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Appendicitis
         subjects affected / exposed
    1 / 58 (1.72%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchitis
         subjects affected / exposed
    0 / 58 (0.00%)
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Catheter site infection
         subjects affected / exposed
    1 / 58 (1.72%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    1 / 58 (1.72%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Clostridium difficile colitis
         subjects affected / exposed
    1 / 58 (1.72%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Device related infection
         subjects affected / exposed
    0 / 58 (0.00%)
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Device related sepsis
         subjects affected / exposed
    1 / 58 (1.72%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Epstein-Barr virus infection
         subjects affected / exposed
    0 / 58 (0.00%)
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Escherichia bacteraemia
         subjects affected / exposed
    1 / 58 (1.72%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis clostridial
         subjects affected / exposed
    1 / 58 (1.72%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peritonitis
         subjects affected / exposed
    0 / 58 (0.00%)
    2 / 56 (3.57%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peritonitis bacterial
         subjects affected / exposed
    1 / 58 (1.72%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    1 / 58 (1.72%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyelonephritis
         subjects affected / exposed
    1 / 58 (1.72%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    1 / 58 (1.72%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Shunt infection
         subjects affected / exposed
    0 / 58 (0.00%)
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Viral infection
         subjects affected / exposed
    1 / 58 (1.72%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    1 / 58 (1.72%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fluid overload
         subjects affected / exposed
    1 / 58 (1.72%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperkalaemia
         subjects affected / exposed
    3 / 58 (5.17%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperphosphataemia
         subjects affected / exposed
    0 / 58 (0.00%)
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Malnutrition
         subjects affected / exposed
    0 / 58 (0.00%)
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Darbepoetin Alfa QW Darbepoetin Alfa Q2W
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    42 / 58 (72.41%)
    43 / 56 (76.79%)
    Investigations
    Blood pressure increased
         subjects affected / exposed
    3 / 58 (5.17%)
    3 / 56 (5.36%)
         occurrences all number
    3
    3
    Injury, poisoning and procedural complications
    Contusion
         subjects affected / exposed
    1 / 58 (1.72%)
    3 / 56 (5.36%)
         occurrences all number
    1
    4
    Procedural hypotension
         subjects affected / exposed
    3 / 58 (5.17%)
    3 / 56 (5.36%)
         occurrences all number
    24
    15
    Vascular disorders
    Hypertension
         subjects affected / exposed
    9 / 58 (15.52%)
    8 / 56 (14.29%)
         occurrences all number
    29
    12
    Hypotension
         subjects affected / exposed
    2 / 58 (3.45%)
    3 / 56 (5.36%)
         occurrences all number
    2
    3
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    3 / 58 (5.17%)
    3 / 56 (5.36%)
         occurrences all number
    3
    3
    Headache
         subjects affected / exposed
    4 / 58 (6.90%)
    10 / 56 (17.86%)
         occurrences all number
    5
    17
    General disorders and administration site conditions
    Catheter site pain
         subjects affected / exposed
    3 / 58 (5.17%)
    1 / 56 (1.79%)
         occurrences all number
    3
    1
    Fatigue
         subjects affected / exposed
    5 / 58 (8.62%)
    2 / 56 (3.57%)
         occurrences all number
    6
    2
    Injection site pain
         subjects affected / exposed
    3 / 58 (5.17%)
    2 / 56 (3.57%)
         occurrences all number
    3
    3
    Medical device complication
         subjects affected / exposed
    2 / 58 (3.45%)
    3 / 56 (5.36%)
         occurrences all number
    2
    3
    Pyrexia
         subjects affected / exposed
    5 / 58 (8.62%)
    10 / 56 (17.86%)
         occurrences all number
    10
    13
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    6 / 58 (10.34%)
    5 / 56 (8.93%)
         occurrences all number
    6
    6
    Abdominal pain upper
         subjects affected / exposed
    3 / 58 (5.17%)
    2 / 56 (3.57%)
         occurrences all number
    3
    2
    Constipation
         subjects affected / exposed
    4 / 58 (6.90%)
    4 / 56 (7.14%)
         occurrences all number
    4
    4
    Diarrhoea
         subjects affected / exposed
    3 / 58 (5.17%)
    4 / 56 (7.14%)
         occurrences all number
    3
    4
    Nausea
         subjects affected / exposed
    5 / 58 (8.62%)
    4 / 56 (7.14%)
         occurrences all number
    6
    4
    Vomiting
         subjects affected / exposed
    10 / 58 (17.24%)
    9 / 56 (16.07%)
         occurrences all number
    12
    13
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    7 / 58 (12.07%)
    4 / 56 (7.14%)
         occurrences all number
    10
    4
    Nasal congestion
         subjects affected / exposed
    4 / 58 (6.90%)
    1 / 56 (1.79%)
         occurrences all number
    4
    1
    Oropharyngeal pain
         subjects affected / exposed
    2 / 58 (3.45%)
    3 / 56 (5.36%)
         occurrences all number
    2
    3
    Skin and subcutaneous tissue disorders
    Pruritus
         subjects affected / exposed
    4 / 58 (6.90%)
    1 / 56 (1.79%)
         occurrences all number
    6
    1
    Rash
         subjects affected / exposed
    3 / 58 (5.17%)
    1 / 56 (1.79%)
         occurrences all number
    5
    1
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    2 / 58 (3.45%)
    3 / 56 (5.36%)
         occurrences all number
    2
    3
    Muscle spasms
         subjects affected / exposed
    5 / 58 (8.62%)
    2 / 56 (3.57%)
         occurrences all number
    5
    3
    Pain in extremity
         subjects affected / exposed
    4 / 58 (6.90%)
    1 / 56 (1.79%)
         occurrences all number
    4
    2
    Infections and infestations
    Catheter site infection
         subjects affected / exposed
    4 / 58 (6.90%)
    3 / 56 (5.36%)
         occurrences all number
    5
    3
    Ear infection
         subjects affected / exposed
    4 / 58 (6.90%)
    0 / 56 (0.00%)
         occurrences all number
    4
    0
    Nasopharyngitis
         subjects affected / exposed
    4 / 58 (6.90%)
    6 / 56 (10.71%)
         occurrences all number
    4
    9
    Pharyngitis
         subjects affected / exposed
    2 / 58 (3.45%)
    5 / 56 (8.93%)
         occurrences all number
    4
    5
    Upper respiratory tract infection
         subjects affected / exposed
    3 / 58 (5.17%)
    7 / 56 (12.50%)
         occurrences all number
    3
    10
    Urinary tract infection
         subjects affected / exposed
    4 / 58 (6.90%)
    0 / 56 (0.00%)
         occurrences all number
    5
    0

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    20 Aug 2007
    The study design was changed from an open-label, single-arm study assessing the safety and efficacy of darbepoetin alfa administered Q2W to a double-blind, randomized, parallel-group study assessing the safety and efficacy of darbepoetin alfa administered QW or Q2W. The objectives, endpoints, procedure, and sample informed consent form were revised to reflect this change. The number of subjects and study centers were increased, and a new region (Canada) was added. In addition, the following changes were made: - The targeted age distribution was revised to enroll a greater percentage of subjects < 12 years. - The Hb target range was revised from 11.0 - 13.0 g/dL to 11.0 - 12.0 g/dL. - Collection of samples for pharmacokinetic analyses was added for subjects < 6 years old. - The frequency of Hb measurements was changed from biweekly to weekly. - Known positive HIV or hepatitis B status was removed from and immunosuppressive agent use was added to the exclusion criteria. The prohibition period for RBC transfusions before randomization was changed from 8 to 12 weeks. - The Epoetin alfa washout period for subjects receiving dialysis was deleted and the prohibition period for any ESA use before randomization was changed from 4 to 12 weeks for all subjects. - Darbepoetin alfa product used in this study was changed from vials to prefilled syringes, and the dosing procedures, including dose adjustment rules, were updated to reflect unit dosing. - Subjects who progressed to dialysis were allowed to remain in the study. In addition, subjects who declined to receive investigational product were allowed to continue with other study procedures. - Analyses sets for efficacy and safety were further defined.
    08 Nov 2007
    The Hb target range was revised to 10.0-12.0 g/dL and the study objectives, endpoints, inclusion criteria, and dose adjustment procedures were updated accordingly. Physical examination procedures were defined in greater detail. The procedures section was updated to reflect the use of a central laboratory for analyses. Language regarding contraception was updated for consistency between the protocol and informed consent template.
    26 Aug 2008
    The following changes were implemented to improve study enrollment: minor updates were made to the eligibility criteria, the number of blood samples collected were reduced by removing samples required for future analysis, and regions outside North America were allowed to participate. The informed consent form template was updated accordingly, and to reflect the most current safety language for darbepoetin alfa and remove Canadian-specific text since Canada was not participating in the study.
    04 May 2010
    The exclusion criteria were revised to allow the use of low dose corticosteroids (such as those used for asthma treatment); this change was implemented to avoid unnecessary exclusion of subjects without altering the study safety for subjects. The informed consent form template was also updated to include additional safety information for darbepoetin alfa from clinical trials.
    30 Jan 2012
    The protocol was primarily amended to allow a 5 μg dose so that subjects who required treatment with < 10 μg darbepoetin alfa (lowest dose previously specified) could receive investigational product. Darbepoetin alfa product was changed from prefilled syringes to vials in order to accommodate this dose while retaining the blind. Dosing procedures, including dose adjustment rules, were updated accordingly. The following changes were also implemented to improve enrollment. - The prohibition period prior to enrollment was changed from 12 to 8 weeks for ESAs and from 12 to 1 week(s) for RBC transfusions. The primary study endpoints were adjusted to account for the shortened period prohibiting RBC transfusions. - The time between consecutive Hb samples was changed from 7 to 5 days for purposes of inclusion - The exclusion criteria for hematologic disease (ie, likely to affect RBC production or turnover) and seizure (ie, nonfebrile) were clarified. - An age group of 1 to < 12 years was added to the subgroup analyses.
    13 Sep 2012
    The protocol was amended to include the occurrence of an unplanned interim analysis of data from all subjects who ended the study by 31 July 2012 in order to fulfill regulatory requirements. In addition, the language regarding serious adverse event reporting was updated, and the sample informed consent was also updated for consistency with current Amgen templates.

    Interruptions (globally)
    Were there any global interruptions to the trial? Yes
    Date
    Interruption
    Restart date
    03 Mar 2014
    Following review of the interim CSR, agreement was reached with both the US FDA (10 July 2012) and the Paediatric Committee (PDCO) of the European Medicines Agency (EMA) (17 January 2014) to terminate the study early on the basis of availability of sufficient data in the targeted population. Study 20050256 was terminated early (last patient completed follow-up 03 March 2014) after enrolling 116 out of 150 planned subjects.
    -

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

    European Medicines Agency © 1995-Tue May 06 15:27:30 CEST 2025 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA