Trial Outcomes & Findings for Study to Assess Darbepoetin Alfa Dosing for the Correction of Anemia in Pediatric Patients With Chronic Kidney Disease (NCT NCT00436748)

Last Updated: 2022-11-29

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

116 participants

Primary outcome timeframe

24 weeks

Results posted on

2022-11-29

Participant Flow

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.

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.

Participant milestones

Participant milestones
Measure	Darbepoetin Alfa QW 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.	Darbepoetin Alfa Q2W 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.
Overall Study STARTED	59	57
Overall Study Received Treatment	58	56
Overall Study COMPLETED	48	45
Overall Study NOT COMPLETED	11	12

Reasons for withdrawal

Reasons for withdrawal
Measure	Darbepoetin Alfa QW 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.	Darbepoetin Alfa Q2W 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.
Overall Study Ineligibility Determined	1	1
Overall Study Adverse Event	0	2
Overall Study Consent Withdrawn	1	4
Overall Study Administrative Decision	1	0
Overall Study Lost to Follow-up	0	1
Overall Study Protocol-specified Criteria	5	4
Overall Study Other	3	0

Baseline Characteristics

Study to Assess Darbepoetin Alfa Dosing for the Correction of Anemia in Pediatric Patients With Chronic Kidney Disease

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Darbepoetin Alfa QW n=58 Participants 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.	Darbepoetin Alfa Q2W n=56 Participants 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.	Total n=114 Participants Total of all reporting groups
Age, Continuous	12.6 years STANDARD_DEVIATION 3.6 • n=5 Participants	12.8 years STANDARD_DEVIATION 3.7 • n=7 Participants	12.7 years STANDARD_DEVIATION 3.6 • n=5 Participants
Age, Customized 1 - < 6 years	2 participants n=5 Participants	1 participants n=7 Participants	3 participants n=5 Participants
Age, Customized 6 - < 12 years	19 participants n=5 Participants	18 participants n=7 Participants	37 participants n=5 Participants
Age, Customized 12 - 18 years	37 participants n=5 Participants	37 participants n=7 Participants	74 participants n=5 Participants
Sex: Female, Male Female	23 Participants n=5 Participants	23 Participants n=7 Participants	46 Participants n=5 Participants
Sex: Female, Male Male	35 Participants n=5 Participants	33 Participants n=7 Participants	68 Participants n=5 Participants
Race/Ethnicity, Customized White or Caucasian	30 participants n=5 Participants	30 participants n=7 Participants	60 participants n=5 Participants
Race/Ethnicity, Customized Black or African American	4 participants n=5 Participants	5 participants n=7 Participants	9 participants n=5 Participants
Race/Ethnicity, Customized Hispanic or Latino	23 participants n=5 Participants	20 participants n=7 Participants	43 participants n=5 Participants
Race/Ethnicity, Customized Other	1 participants n=5 Participants	1 participants n=7 Participants	2 participants n=5 Participants
Dialysis Status Not receiving dialysis	33 participants n=5 Participants	33 participants n=7 Participants	66 participants n=5 Participants
Dialysis Status Receiving hemodialysis	15 participants n=5 Participants	14 participants n=7 Participants	29 participants n=5 Participants
Dialysis Status Receiving peritoneal dialysis	10 participants n=5 Participants	9 participants n=7 Participants	19 participants n=5 Participants
Hemoglobin Concentration	8.59 g/dL STANDARD_DEVIATION 0.84 • n=5 Participants	8.73 g/dL STANDARD_DEVIATION 0.84 • n=7 Participants	8.66 g/dL STANDARD_DEVIATION 0.84 • n=5 Participants

PRIMARY outcome

Timeframe: 24 weeks

Population: Efficacy analysis set

Outcome measures

Outcome measures
Measure	Darbepoetin Alfa QW n=58 Participants 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.	Darbepoetin Alfa Q2W n=56 Participants 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.
Proportion of Participants Achieving Hemoglobin ≥ 10.0 g/dL	0.983 proportion of participants Interval 0.908 to 1.0	0.839 proportion of participants Interval 0.717 to 0.924

SECONDARY outcome

Timeframe: 24 weeks

Population: Efficacy analysis set responders (participants with at least 1 postbaseline hemoglobin ≥ 10.0 g/dL)

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.

Outcome measures

Outcome measures
Measure	Darbepoetin Alfa QW n=57 Participants 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.	Darbepoetin Alfa Q2W n=47 Participants 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.
Time to First Hemoglobin Value ≥ 10.0 g/dL	24.0 days Interval 15.0 to 50.0	22.0 days Interval 14.0 to 41.0

SECONDARY outcome

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.

Population: Efficacy analyis set with available data at each time point (indicated by "n").

Outcome measures

Outcome measures
Measure	Darbepoetin Alfa QW n=58 Participants 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.	Darbepoetin Alfa Q2W n=56 Participants 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.
Hemoglobin Concentration Over Time Week 16 (n=48, 47)	11.36 g/dL Standard Deviation 1.19	10.86 g/dL Standard Deviation 1.21
Hemoglobin Concentration Over Time Week 17 (n=48, 48)	11.21 g/dL Standard Deviation 1.23	11.05 g/dL Standard Deviation 1.00
Hemoglobin Concentration Over Time Week 18 (n=49, 46)	11.14 g/dL Standard Deviation 1.20	10.91 g/dL Standard Deviation 1.09
Hemoglobin Concentration Over Time Week 19 (n=48, 46)	11.06 g/dL Standard Deviation 0.91	10.91 g/dL Standard Deviation 1.09
Hemoglobin Concentration Over Time Week 23 (n=48, 44)	10.93 g/dL Standard Deviation 1.10	10.50 g/dL Standard Deviation 1.05
Hemoglobin Concentration Over Time Baseline (n=58, 56)	8.59 g/dL Standard Deviation 0.84	8.73 g/dL Standard Deviation 0.84
Hemoglobin Concentration Over Time Week 1 (n=53, 50)	8.64 g/dL Standard Deviation 0.90	8.65 g/dL Standard Deviation 0.95
Hemoglobin Concentration Over Time Week 2 (n=52, 52)	8.74 g/dL Standard Deviation 1.09	8.96 g/dL Standard Deviation 1.20
Hemoglobin Concentration Over Time Week 3 (n=51, 55)	9.28 g/dL Standard Deviation 1.27	9.09 g/dL Standard Deviation 1.27
Hemoglobin Concentration Over Time Week 4 (n=53, 53)	9.79 g/dL Standard Deviation 1.30	9.55 g/dL Standard Deviation 1.23
Hemoglobin Concentration Over Time Week 5 (n=53, 52)	10.18 g/dL Standard Deviation 1.29	9.87 g/dL Standard Deviation 1.32
Hemoglobin Concentration Over Time Week 6 (n=54, 50)	10.54 g/dL Standard Deviation 1.43	10.19 g/dL Standard Deviation 1.33
Hemoglobin Concentration Over Time Week 7 (n=52, 48)	10.96 g/dL Standard Deviation 1.53	10.17 g/dL Standard Deviation 1.25
Hemoglobin Concentration Over Time Week 8 (n=53, 51)	11.05 g/dL Standard Deviation 1.37	10.47 g/dL Standard Deviation 1.21
Hemoglobin Concentration Over Time Week 9 (n=50, 51)	11.03 g/dL Standard Deviation 1.48	10.60 g/dL Standard Deviation 1.34
Hemoglobin Concentration Over Time Week 10 (n=54, 51)	11.32 g/dL Standard Deviation 1.33	10.60 g/dL Standard Deviation 1.29
Hemoglobin Concentration Over Time Week 11 (n=51, 48)	11.34 g/dL Standard Deviation 1.33	10.73 g/dL Standard Deviation 1.22
Hemoglobin Concentration Over Time Week 12 (n=51, 48)	11.45 g/dL Standard Deviation 1.25	10.87 g/dL Standard Deviation 1.38
Hemoglobin Concentration Over Time Week 13 (n=50, 47)	11.68 g/dL Standard Deviation 1.19	10.82 g/dL Standard Deviation 1.33
Hemoglobin Concentration Over Time Week 14 (n=52, 50)	11.27 g/dL Standard Deviation 1.28	10.92 g/dL Standard Deviation 1.31
Hemoglobin Concentration Over Time Week 15 (n=49, 50)	11.25 g/dL Standard Deviation 1.13	11.00 g/dL Standard Deviation 1.23
Hemoglobin Concentration Over Time Week 20 (n=48, 45)	11.09 g/dL Standard Deviation 1.03	10.76 g/dL Standard Deviation 1.00
Hemoglobin Concentration Over Time Week 21 (n=48, 46)	11.20 g/dL Standard Deviation 1.04	10.64 g/dL Standard Deviation 0.99
Hemoglobin Concentration Over Time Week 22 (n=48, 45)	11.00 g/dL Standard Deviation 1.19	10.58 g/dL Standard Deviation 1.04
Hemoglobin Concentration Over Time Week 24 (n=45, 46)	10.93 g/dL Standard Deviation 1.16	10.43 g/dL Standard Deviation 0.97
Hemoglobin Concentration Over Time Week 25 (n= 32, 31)	11.13 g/dL Standard Deviation 1.10	10.65 g/dL Standard Deviation 0.75

SECONDARY outcome

Timeframe: 24 weeks

Population: Efficacy analysis set responders (participants with at least 1 postbaseline hemoglobin ≥ 10.0 g/dL) for whom dosing data were available.

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.

Outcome measures

Outcome measures
Measure	Darbepoetin Alfa QW n=54 Participants 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.	Darbepoetin Alfa Q2W n=44 Participants 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.
Weight-adjusted Darbepoetin Alfa Dose at Time of Achieving First Hemoglobin ≥ 10.0 g/dL	0.48 μg/kg Standard Deviation 0.24	0.76 μg/kg Standard Deviation 0.21

SECONDARY outcome

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.

Population: Efficacy analyis set with available data at each time point (indicated by "n"). 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).

Arithmetic means are provided; Withheld doses are counted as 0 μg.

Outcome measures

Outcome measures
Measure	Darbepoetin Alfa QW n=58 Participants 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.	Darbepoetin Alfa Q2W n=56 Participants 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.
Darbepoetin Alfa Weight-Adjusted Dose Over Time Week 23 (n=47, 44)	0.39 μg/kg Standard Deviation 0.63	0.49 μg/kg Standard Deviation 0.40
Darbepoetin Alfa Weight-Adjusted Dose Over Time Initial Dose (n=58, 56)	0.45 μg/kg Standard Deviation 0.07	0.73 μg/kg Standard Deviation 0.13
Darbepoetin Alfa Weight-Adjusted Dose Over Time Week 2 (n=55, 0)	0.45 μg/kg Standard Deviation 0.07	NA μg/kg Standard Deviation NA Participants received dosing every 2 weeks
Darbepoetin Alfa Weight-Adjusted Dose Over Time Week 3 (n=55, 52)	0.44 μg/kg Standard Deviation 0.07	0.72 μg/kg Standard Deviation 0.11
Darbepoetin Alfa Weight-Adjusted Dose Over Time Week 4 (n=54, 0)	0.40 μg/kg Standard Deviation 0.11	NA μg/kg Standard Deviation NA Participants received dosing every 2 weeks
Darbepoetin Alfa Weight-Adjusted Dose Over Time Week 5 (n=54, 51)	0.43 μg/kg Standard Deviation 0.26	0.72 μg/kg Standard Deviation 0.25
Darbepoetin Alfa Weight-Adjusted Dose Over Time Week 6 (n=54, 0)	0.42 μg/kg Standard Deviation 0.29	NA μg/kg Standard Deviation NA Participants received dosing every 2 weeks
Darbepoetin Alfa Weight-Adjusted Dose Over Time Week 7 (n=54, 51)	0.38 μg/kg Standard Deviation 0.25	0.70 μg/kg Standard Deviation 0.28
Darbepoetin Alfa Weight-Adjusted Dose Over Time Week 8 (n=53, 1)	0.34 μg/kg Standard Deviation 0.24	0.00 μg/kg Standard Deviation NA Could not be calculated since sample size = 1
Darbepoetin Alfa Weight-Adjusted Dose Over Time Week 9 (n=52, 52)	0.32 μg/kg Standard Deviation 0.23	0.64 μg/kg Standard Deviation 0.26
Darbepoetin Alfa Weight-Adjusted Dose Over Time Week 10 (n=55, 3)	0.33 μg/kg Standard Deviation 0.26	0.00 μg/kg Standard Deviation 0.00
Darbepoetin Alfa Weight-Adjusted Dose Over Time Week 11 (n=54, 50)	0.32 μg/kg Standard Deviation 0.28	0.61 μg/kg Standard Deviation 0.35
Darbepoetin Alfa Weight-Adjusted Dose Over Time Week 12 (n=54, 2)	0.26 μg/kg Standard Deviation 0.28	0.00 μg/kg Standard Deviation 0.00
Darbepoetin Alfa Weight-Adjusted Dose Over Time Week 13 (n=54, 50)	0.24 μg/kg Standard Deviation 0.28	0.56 μg/kg Standard Deviation 0.35
Darbepoetin Alfa Weight-Adjusted Dose Over Time Week 14 (n=53, 4)	0.21 μg/kg Standard Deviation 0.27	0.00 μg/kg Standard Deviation 0.00
Darbepoetin Alfa Weight-Adjusted Dose Over Time Week 15 (n=52, 48)	0.31 μg/kg Standard Deviation 0.33	0.53 μg/kg Standard Deviation 0.36
Darbepoetin Alfa Weight-Adjusted Dose Over Time Week 16 (n=50, 5)	0.35 μg/kg Standard Deviation 0.44	0.00 μg/kg Standard Deviation 0.00
Darbepoetin Alfa Weight-Adjusted Dose Over Time Week 17 (n=51, 47)	0.29 μg/kg Standard Deviation 0.34	0.61 μg/kg Standard Deviation 0.97
Darbepoetin Alfa Weight-Adjusted Dose Over Time Week 18 (n=50, 3)	0.32 μg/kg Standard Deviation 0.40	0.00 μg/kg Standard Deviation 0.00
Darbepoetin Alfa Weight-Adjusted Dose Over Time Week 19 (n=50, 46)	0.31 μg/kg Standard Deviation 0.33	0.45 μg/kg Standard Deviation 0.30
Darbepoetin Alfa Weight-Adjusted Dose Over Time Week 20 (n=48, 4)	0.35 μg/kg Standard Deviation 0.34	0.00 μg/kg Standard Deviation 0.00
Darbepoetin Alfa Weight-Adjusted Dose Over Time Week 21 (n=48, 46)	0.38 μg/kg Standard Deviation 0.63	0.47 μg/kg Standard Deviation 0.36
Darbepoetin Alfa Weight-Adjusted Dose Over Time Week 22 (n=48, 3)	0.38 μg/kg Standard Deviation 0.64	0.00 μg/kg Standard Deviation 0.00
Darbepoetin Alfa Weight-Adjusted Dose Over Time Week 24 (n=46, 1)	0.41 μg/kg Standard Deviation 0.63	0.00 μg/kg Standard Deviation NA Could not be calculated since sample size = 1

SECONDARY outcome

Timeframe: Baseline, Week 13 and Week 25 (or end of study visit if earlier than Week 25)

Population: Efficacy analysis set with available data for each score at each time point (indicated by "n").

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).

Outcome measures

Outcome measures
Measure	Darbepoetin Alfa QW n=45 Participants 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.	Darbepoetin Alfa Q2W n=46 Participants 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.
Change From Baseline at Week 13 and Week 25 in Parent-reported Pediatric Quality of Life Inventory (PedsQL) Scores Week 13 Physical function score (n=45, 46)	3.61 units on a scale Standard Error 3.20	2.31 units on a scale Standard Error 3.35
Change From Baseline at Week 13 and Week 25 in Parent-reported Pediatric Quality of Life Inventory (PedsQL) Scores Week 25 Total Score (n=38, 41)	1.90 units on a scale Standard Error 2.06	0.65 units on a scale Standard Error 2.66
Change From Baseline at Week 13 and Week 25 in Parent-reported Pediatric Quality of Life Inventory (PedsQL) Scores Week 25 Physical function score (n=38, 41)	0.66 units on a scale Standard Error 3.89	5.18 units on a scale Standard Error 3.59
Change From Baseline at Week 13 and Week 25 in Parent-reported Pediatric Quality of Life Inventory (PedsQL) Scores Week 13 Total Score (n=45, 46)	4.50 units on a scale Standard Error 2.19	0.58 units on a scale Standard Error 2.43
Change From Baseline at Week 13 and Week 25 in Parent-reported Pediatric Quality of Life Inventory (PedsQL) Scores Week 13 Psychosocial composite score (n=45, 46)	5.12 units on a scale Standard Error 2.16	-0.41 units on a scale Standard Error 2.57
Change From Baseline at Week 13 and Week 25 in Parent-reported Pediatric Quality of Life Inventory (PedsQL) Scores Week 13 Emotional function score (n=45, 46)	1.00 units on a scale Standard Error 3.00	-3.89 units on a scale Standard Error 2.74
Change From Baseline at Week 13 and Week 25 in Parent-reported Pediatric Quality of Life Inventory (PedsQL) Scores Week 13 Social function score (n=45, 46)	6.89 units on a scale Standard Error 3.54	0.76 units on a scale Standard Error 3.56
Change From Baseline at Week 13 and Week 25 in Parent-reported Pediatric Quality of Life Inventory (PedsQL) Scores Week 13 School function score (n=42, 42)	7.30 units on a scale Standard Error 2.47	4.17 units on a scale Standard Error 3.63
Change From Baseline at Week 13 and Week 25 in Parent-reported Pediatric Quality of Life Inventory (PedsQL) Scores Week 25 Psychosocial composite score (n=38, 41)	2.52 units on a scale Standard Error 1.83	-1.84 units on a scale Standard Error 3.13
Change From Baseline at Week 13 and Week 25 in Parent-reported Pediatric Quality of Life Inventory (PedsQL) Scores Week 25 Emotional function score (n=38, 41)	-0.66 units on a scale Standard Error 2.61	-3.51 units on a scale Standard Error 3.16
Change From Baseline at Week 13 and Week 25 in Parent-reported Pediatric Quality of Life Inventory (PedsQL) Scores Week 25 Social function score (n=38, 41)	5.13 units on a scale Standard Error 2.64	-2.20 units on a scale Standard Error 4.10
Change From Baseline at Week 13 and Week 25 in Parent-reported Pediatric Quality of Life Inventory (PedsQL) Scores Week 25 School function score (n=36, 37)	3.90 units on a scale Standard Error 2.51	2.03 units on a scale Standard Error 3.94

SECONDARY outcome

Timeframe: Baseline, Week 13 and Week 25 (or end of study visit if earlier than Week 25)

Population: Efficacy analysis set aged \> 5 years and with available data for each score at each time point (indicated by "n").

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).

Outcome measures

Outcome measures
Measure	Darbepoetin Alfa QW n=46 Participants 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.	Darbepoetin Alfa Q2W n=46 Participants 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.
Change From Baseline at Week 13 and Week 25 in Child Self-reported Pediatric Quality of Life Inventory (PedsQL) Scores Week 25 Physical function score (n=40, 42)	7.42 units on a scale Standard Error 2.48	0.74 units on a scale Standard Error 2.80
Change From Baseline at Week 13 and Week 25 in Child Self-reported Pediatric Quality of Life Inventory (PedsQL) Scores Week 13 Total Score (n=46, 46)	2.94 units on a scale Standard Error 1.70	-1.23 units on a scale Standard Error 2.04
Change From Baseline at Week 13 and Week 25 in Child Self-reported Pediatric Quality of Life Inventory (PedsQL) Scores Week 13 Psychosocial composite score (n=46, 46)	2.59 units on a scale Standard Error 1.92	-0.45 units on a scale Standard Error 2.23
Change From Baseline at Week 13 and Week 25 in Child Self-reported Pediatric Quality of Life Inventory (PedsQL) Scores Week 13 Physical function score (n=46, 46)	3.78 units on a scale Standard Error 2.43	-2.79 units on a scale Standard Error 2.59
Change From Baseline at Week 13 and Week 25 in Child Self-reported Pediatric Quality of Life Inventory (PedsQL) Scores Week 13 Emotional function score (n=46, 46)	0.43 units on a scale Standard Error 2.52	-0.76 units on a scale Standard Error 2.79
Change From Baseline at Week 13 and Week 25 in Child Self-reported Pediatric Quality of Life Inventory (PedsQL) Scores Week 13 Social function score (n=46, 46)	3.26 units on a scale Standard Error 2.93	-2.28 units on a scale Standard Error 3.02
Change From Baseline at Week 13 and Week 25 in Child Self-reported Pediatric Quality of Life Inventory (PedsQL) Scores Week 13 School function score (n=45, 43)	2.89 units on a scale Standard Error 2.98	2.44 units on a scale Standard Error 3.83
Change From Baseline at Week 13 and Week 25 in Child Self-reported Pediatric Quality of Life Inventory (PedsQL) Scores Week 25 Total Score (n=40, 42)	5.00 units on a scale Standard Error 1.75	2.58 units on a scale Standard Error 1.78
Change From Baseline at Week 13 and Week 25 in Child Self-reported Pediatric Quality of Life Inventory (PedsQL) Scores Week 25 Psychosocial composite score (n=40, 42)	3.81 units on a scale Standard Error 1.97	3.53 units on a scale Standard Error 2.01
Change From Baseline at Week 13 and Week 25 in Child Self-reported Pediatric Quality of Life Inventory (PedsQL) Scores Week 25 Emotional function score (n=40, 42)	-0.25 units on a scale Standard Error 2.51	3.93 units on a scale Standard Error 3.10
Change From Baseline at Week 13 and Week 25 in Child Self-reported Pediatric Quality of Life Inventory (PedsQL) Scores Week 25 Social function score (n=40, 42)	7.00 units on a scale Standard Error 3.10	2.50 units on a scale Standard Error 2.67
Change From Baseline at Week 13 and Week 25 in Child Self-reported Pediatric Quality of Life Inventory (PedsQL) Scores Week 25 School function score (n=40, 39)	4.25 units on a scale Standard Error 3.14	3.85 units on a scale Standard Error 3.09

SECONDARY outcome

Timeframe: 25 weeks

Population: Safety analysis set including all participants who received ≥ 1 dose of investigational product.

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.

Outcome measures

Outcome measures
Measure	Darbepoetin Alfa QW n=58 Participants 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.	Darbepoetin Alfa Q2W n=56 Participants 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.
Number of Participants With Treatment-emergent Adverse Events Serious adverse events	16 participants	14 participants
Number of Participants With Treatment-emergent Adverse Events TRAE leading to discontinuation of IP	0 participants	2 participants
Number of Participants With Treatment-emergent Adverse Events All adverse events	48 participants	50 participants
Number of Participants With Treatment-emergent Adverse Events Leading to discontinuation of IP	0 participants	2 participants
Number of Participants With Treatment-emergent Adverse Events Leading to discontinuation from study	0 participants	2 participants
Number of Participants With Treatment-emergent Adverse Events Fatal adverse events	0 participants	0 participants
Number of Participants With Treatment-emergent Adverse Events Events of interest	18 participants	20 participants
Number of Participants With Treatment-emergent Adverse Events Treatment-related adverse events (TRAE)	14 participants	16 participants
Number of Participants With Treatment-emergent Adverse Events Treatment-related serious adverse events	1 participants	2 participants
Number of Participants With Treatment-emergent Adverse Events TRAE leading to discontinuation from study	0 participants	2 participants
Number of Participants With Treatment-emergent Adverse Events Treatment-related fatal adverse events	0 participants	0 participants
Number of Participants With Treatment-emergent Adverse Events Treatment-related events of interest	6 participants	9 participants

SECONDARY outcome

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.

Population: Safety analyis set with available data at each time point (indicated by "n").

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.

Outcome measures

Outcome measures
Measure	Darbepoetin Alfa QW n=58 Participants 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.	Darbepoetin Alfa Q2W n=56 Participants 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.
Hemoglobin Serial Rate of Change (ROC) Over Time Week 2 (n=49, 47)	0.263 g/dL/week Full Range 1.09 • Interval -0.9 to 1.17	0.350 g/dL/week Full Range 1.20 • Interval -1.82 to 2.1
Hemoglobin Serial Rate of Change (ROC) Over Time Week 3 (n=50, 53)	0.530 g/dL/week Full Range 1.27 • Interval -1.0 to 1.7	0.200 g/dL/week Full Range 1.27 • Interval -1.23 to 1.4
Hemoglobin Serial Rate of Change (ROC) Over Time Week 23 (n=47, 43)	-0.100 g/dL/week Full Range 1.10 • Interval -2.8 to 1.75	0.000 g/dL/week Full Range 1.05 • Interval -1.54 to 1.82
Hemoglobin Serial Rate of Change (ROC) Over Time Week 24 (n=44, 46)	0.100 g/dL/week Full Range 1.16 • Interval -3.03 to 4.34	0.050 g/dL/week Full Range 0.97 • Interval -1.6 to 6.44
Hemoglobin Serial Rate of Change (ROC) Over Time Week 4 (n=53, 52)	0.560 g/dL/week Full Range 1.30 • Interval -0.4 to 2.2	0.513 g/dL/week Full Range 1.23 • Interval -1.6 to 3.33
Hemoglobin Serial Rate of Change (ROC) Over Time Week 5 (n=53, 49)	0.438 g/dL/week Full Range 1.29 • Interval -2.0 to 2.0	0.117 g/dL/week Full Range 1.32 • Interval -3.92 to 1.52
Hemoglobin Serial Rate of Change (ROC) Over Time Week 6 (n=54, 48)	0.400 g/dL/week Full Range 1.43 • Interval -2.5 to 2.4	0.231 g/dL/week Full Range 1.33 • Interval -1.05 to 2.4
Hemoglobin Serial Rate of Change (ROC) Over Time Week 7 (n=51, 45)	0.200 g/dL/week Full Range 1.53 • Interval -1.2 to 2.9	0.100 g/dL/week Full Range 1.25 • Interval -1.75 to 2.57
Hemoglobin Serial Rate of Change (ROC) Over Time Week 8 (n=52, 49)	0.163 g/dL/week Full Range 1.37 • Interval -1.98 to 1.63	0.300 g/dL/week Full Range 1.21 • Interval -2.71 to 1.17
Hemoglobin Serial Rate of Change (ROC) Over Time Week 9 (n=49, 50)	0.100 g/dL/week Full Range 1.48 • Interval -2.8 to 1.4	0.089 g/dL/week Full Range 1.34 • Interval -1.3 to 2.2
Hemoglobin Serial Rate of Change (ROC) Over Time Week 10 (n=53, 50)	0.117 g/dL/week Full Range 1.33 • Interval -1.4 to 3.9	0.000 g/dL/week Full Range 1.29 • Interval -2.1 to 1.52
Hemoglobin Serial Rate of Change (ROC) Over Time Week 11 (n=51, 48)	0.100 g/dL/week Full Range 1.33 • Interval -2.1 to 1.87	0.138 g/dL/week Full Range 1.22 • Interval -1.49 to 1.49
Hemoglobin Serial Rate of Change (ROC) Over Time Week 12 (n=51, 48)	0.000 g/dL/week Full Range 1.25 • Interval -1.4 to 4.4	0.200 g/dL/week Full Range 1.38 • Interval -2.2 to 1.1
Hemoglobin Serial Rate of Change (ROC) Over Time Week 13 (n=50, 47)	0.128 g/dL/week Full Range 1.19 • Interval -2.8 to 2.7	-0.064 g/dL/week Full Range 1.33 • Interval -2.57 to 2.19
Hemoglobin Serial Rate of Change (ROC) Over Time Week 14 (n=52, 50)	-0.419 g/dL/week Full Range 1.28 • Interval -1.87 to 2.4	0.023 g/dL/week Full Range 1.31 • Interval -1.4 to 1.4
Hemoglobin Serial Rate of Change (ROC) Over Time Week 15 (n=49, 50)	0.200 g/dL/week Full Range 1.13 • Interval -1.6 to 2.33	0.128 g/dL/week Full Range 1.23 • Interval -2.38 to 1.63
Hemoglobin Serial Rate of Change (ROC) Over Time Week 16 (n=48, 47)	0.000 g/dL/week Full Range 1.19 • Interval -2.1 to 3.27	-0.100 g/dL/week Full Range 1.21 • Interval -3.2 to 1.1
Hemoglobin Serial Rate of Change (ROC) Over Time Week 17 (n=47, 48)	-0.100 g/dL/week Full Range 1.23 • Interval -2.8 to 2.4	0.139 g/dL/week Full Range 1.00 • Interval -1.0 to 2.0
Hemoglobin Serial Rate of Change (ROC) Over Time Week 18 (n=48, 46)	-0.188 g/dL/week Full Range 1.20 • Interval -2.3 to 1.4	0.094 g/dL/week Full Range 1.09 • Interval -2.33 to 1.4
Hemoglobin Serial Rate of Change (ROC) Over Time Week 19 (n=47, 46)	0.100 g/dL/week Full Range 0.91 • Interval -1.52 to 1.2	-0.100 g/dL/week Full Range 1.09 • Interval -2.22 to 3.9
Hemoglobin Serial Rate of Change (ROC) Over Time Week 20 (n=47, 44)	0.000 g/dL/week Full Range 1.03 • Interval -1.9 to 2.6	-0.050 g/dL/week Full Range 1.00 • Interval -3.2 to 1.1
Hemoglobin Serial Rate of Change (ROC) Over Time Week 21 (n=47, 45)	0.100 g/dL/week Full Range 1.04 • Interval -1.48 to 2.45	-0.140 g/dL/week Full Range 0.99 • Interval -1.2 to 1.4
Hemoglobin Serial Rate of Change (ROC) Over Time Week 22 (n=48, 44)	-0.200 g/dL/week Full Range 1.19 • Interval -2.6 to 1.1	0.000 g/dL/week Full Range 1.04 • Interval -1.7 to 1.6
Hemoglobin Serial Rate of Change (ROC) Over Time Week 25 (n=32, 31)	0.188 g/dL/week Full Range 1.10 • Interval -1.2 to 2.1	0.000 g/dL/week Full Range 0.75 • Interval -1.05 to 1.68

SECONDARY outcome

Timeframe: 25 weeks

Population: Safety analysis set

Outcome measures

Outcome measures
Measure	Darbepoetin Alfa QW n=58 Participants 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.	Darbepoetin Alfa Q2W n=56 Participants 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.
Number of Participants With Hemoglobin > 12.0, > 13.0, and > 14.0 g/dL During the Study Number of participants with hemoglobin > 12.0 g/dL	44 participants	33 participants
Number of Participants With Hemoglobin > 12.0, > 13.0, and > 14.0 g/dL During the Study Number of participants with hemoglobin > 13.0 g/dL	24 participants	6 participants
Number of Participants With Hemoglobin > 12.0, > 13.0, and > 14.0 g/dL During the Study Number of participants with hemoglobin > 14.0 g/dL	6 participants	2 participants

SECONDARY outcome

Timeframe: 25 weeks

Population: Safety analysis set

The maximum increase between any 2 non-missing hemoglobin measurements over any 2-week period from Day 1.

Outcome measures

Outcome measures
Measure	Darbepoetin Alfa QW n=58 Participants 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.	Darbepoetin Alfa Q2W n=56 Participants 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.
Maximum Increase in Hemoglobin Over Any 2 Week Period	2.06 g/dL/2 weeks Standard Deviation 0.88	1.61 g/dL/2 weeks Standard Deviation 0.76

SECONDARY outcome

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.

Population: Safety analyis set with available data at each time point (indicated by "n").

Outcome measures

Outcome measures
Measure	Darbepoetin Alfa QW n=58 Participants 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.	Darbepoetin Alfa Q2W n=56 Participants 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.
Change From Baseline in Systolic Blood Pressure Over Time Week 2 (n=55, 54)	1.7 mmHg Standard Deviation 11.6 • Interval -0.9 to 1.17	-3.9 mmHg Standard Deviation 11.1 • Interval -1.82 to 2.1
Change From Baseline in Systolic Blood Pressure Over Time Week 3 (n=55, 56)	1.1 mmHg Standard Deviation 14.1 • Interval -1.0 to 1.7	0.0 mmHg Standard Deviation 12.7 • Interval -1.23 to 1.4
Change From Baseline in Systolic Blood Pressure Over Time Week 4 (n=55, 54)	1.3 mmHg Standard Deviation 13.0 • Interval -0.4 to 2.2	1.2 mmHg Standard Deviation 11.5 • Interval -1.6 to 3.33
Change From Baseline in Systolic Blood Pressure Over Time Week 5 (n=55, 52)	1.1 mmHg Standard Deviation 13.7 • Interval -2.0 to 2.0	-3.0 mmHg Standard Deviation 13.7 • Interval -3.92 to 1.52
Change From Baseline in Systolic Blood Pressure Over Time Week 6 (n=54, 51)	0.2 mmHg Standard Deviation 14.2 • Interval -2.5 to 2.4	-2.9 mmHg Standard Deviation 12.5 • Interval -1.05 to 2.4
Change From Baseline in Systolic Blood Pressure Over Time Week 7 (n=54, 52)	-1.0 mmHg Standard Deviation 14.2 • Interval -1.2 to 2.9	-3.7 mmHg Standard Deviation 13.4 • Interval -1.75 to 2.57
Change From Baseline in Systolic Blood Pressure Over Time Week 8 (n=55, 52)	0.5 mmHg Standard Deviation 16.0 • Interval -1.98 to 1.63	-2.7 mmHg Standard Deviation 13.8 • Interval -2.71 to 1.17
Change From Baseline in Systolic Blood Pressure Over Time Week 9 (n=54, 52)	1.0 mmHg Standard Deviation 18.3 • Interval -2.8 to 1.4	-3.1 mmHg Standard Deviation 14.5 • Interval -1.3 to 2.2
Change From Baseline in Systolic Blood Pressure Over Time Week 10 (n=55, 52)	-0.2 mmHg Standard Deviation 16.6 • Interval -1.4 to 3.9	-3.7 mmHg Standard Deviation 14.6 • Interval -2.1 to 1.52
Change From Baseline in Systolic Blood Pressure Over Time Week 11 (n=54, 51)	-2.0 mmHg Standard Deviation 15.6 • Interval -2.1 to 1.87	-1.8 mmHg Standard Deviation 15.9 • Interval -1.49 to 1.49
Change From Baseline in Systolic Blood Pressure Over Time Week 12 (n=55, 49)	-2.4 mmHg Standard Deviation 17.2 • Interval -1.4 to 4.4	-2.8 mmHg Standard Deviation 15.4 • Interval -2.2 to 1.1
Change From Baseline in Systolic Blood Pressure Over Time Week 13 (n=53, 50)	0.5 mmHg Standard Deviation 14.8 • Interval -2.8 to 2.7	-2.1 mmHg Standard Deviation 14.2 • Interval -2.57 to 2.19
Change From Baseline in Systolic Blood Pressure Over Time Week 14 (n=54, 50)	-2.3 mmHg Standard Deviation 19.5 • Interval -1.87 to 2.4	-1.8 mmHg Standard Deviation 15.8 • Interval -1.4 to 1.4
Change From Baseline in Systolic Blood Pressure Over Time Week 15 (n=53, 50)	0.1 mmHg Standard Deviation 17.4 • Interval -1.6 to 2.33	-2.4 mmHg Standard Deviation 13.0 • Interval -2.38 to 1.63
Change From Baseline in Systolic Blood Pressure Over Time Week 16 (n=50, 48)	1.9 mmHg Standard Deviation 16.4 • Interval -2.1 to 3.27	-3.8 mmHg Standard Deviation 16.3 • Interval -3.2 to 1.1
Change From Baseline in Systolic Blood Pressure Over Time Week 17 (n=51, 47)	1.0 mmHg Standard Deviation 17.7 • Interval -2.8 to 2.4	0.1 mmHg Standard Deviation 10.6 • Interval -1.0 to 2.0
Change From Baseline in Systolic Blood Pressure Over Time Week 18 (n=50, 46)	0.5 mmHg Standard Deviation 18.5 • Interval -2.3 to 1.4	0.0 mmHg Standard Deviation 15.5 • Interval -2.33 to 1.4
Change From Baseline in Systolic Blood Pressure Over Time Week 19 (n=50, 47)	3.4 mmHg Standard Deviation 16.0 • Interval -1.52 to 1.2	-2.5 mmHg Standard Deviation 14.2 • Interval -2.22 to 3.9
Change From Baseline in Systolic Blood Pressure Over Time Week 20 (n=48, 46)	-0.9 mmHg Standard Deviation 18.3 • Interval -1.9 to 2.6	-4.0 mmHg Standard Deviation 13.0 • Interval -3.2 to 1.1
Change From Baseline in Systolic Blood Pressure Over Time Week 21 (n=49, 46)	1.9 mmHg Standard Deviation 15.7 • Interval -1.48 to 2.45	-2.2 mmHg Standard Deviation 15.0 • Interval -1.2 to 1.4
Change From Baseline in Systolic Blood Pressure Over Time Week 22 (n=48, 46)	-0.6 mmHg Standard Deviation 18.2 • Interval -2.6 to 1.1	-0.9 mmHg Standard Deviation 15.0 • Interval -1.7 to 1.6
Change From Baseline in Systolic Blood Pressure Over Time Week 23 (n=47, 45)	-0.6 mmHg Standard Deviation 16.5 • Interval -2.8 to 1.75	-1.2 mmHg Standard Deviation 15.7 • Interval -1.54 to 1.82
Change From Baseline in Systolic Blood Pressure Over Time Week 24 (n=46, 46)	0.0 mmHg Standard Deviation 17.8 • Interval -3.03 to 4.34	-2.0 mmHg Standard Deviation 11.8 • Interval -1.6 to 6.44
Change From Baseline in Systolic Blood Pressure Over Time Week 25 (n=34, 32)	-0.5 mmHg Standard Deviation 14.3 • Interval -1.2 to 2.1	-2.3 mmHg Standard Deviation 12.4 • Interval -1.05 to 1.68

SECONDARY outcome

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.

Population: Safety analyis set with available data at each time point (indicated by "n").

Outcome measures

Outcome measures
Measure	Darbepoetin Alfa QW n=58 Participants 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.	Darbepoetin Alfa Q2W n=56 Participants 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.
Change From Baseline in Diastolic Blood Pressure Over Time Week 11 (n=54, 51)	3.9 mmHg Standard Deviation 11.8 • Interval -2.1 to 1.87	0.9 mmHg Standard Deviation 14.4 • Interval -1.49 to 1.49
Change From Baseline in Diastolic Blood Pressure Over Time Week 12 (n=55, 49)	1.6 mmHg Standard Deviation 10.4 • Interval -1.4 to 4.4	2.8 mmHg Standard Deviation 13.7 • Interval -2.2 to 1.1
Change From Baseline in Diastolic Blood Pressure Over Time Week 25 (n=34, 32)	3.0 mmHg Standard Deviation 13.0 • Interval -1.2 to 2.1	-1.5 mmHg Standard Deviation 10.7 • Interval -1.05 to 1.68
Change From Baseline in Diastolic Blood Pressure Over Time Week 2 (n=55, 54)	1.4 mmHg Standard Deviation 9.4 • Interval -0.9 to 1.17	0.8 mmHg Standard Deviation 11.1 • Interval -1.82 to 2.1
Change From Baseline in Diastolic Blood Pressure Over Time Week 3 (n=55, 56)	2.2 mmHg Standard Deviation 11.0 • Interval -1.0 to 1.7	3.1 mmHg Standard Deviation 10.8 • Interval -1.23 to 1.4
Change From Baseline in Diastolic Blood Pressure Over Time Week 4 (n=55, 54)	2.8 mmHg Standard Deviation 11.0 • Interval -0.4 to 2.2	1.8 mmHg Standard Deviation 12.6 • Interval -1.6 to 3.33
Change From Baseline in Diastolic Blood Pressure Over Time Week 5 (n=55, 52)	3.0 mmHg Standard Deviation 12.4 • Interval -2.0 to 2.0	-0.2 mmHg Standard Deviation 11.2 • Interval -3.92 to 1.52
Change From Baseline in Diastolic Blood Pressure Over Time Week 6 (n=54, 51)	2.6 mmHg Standard Deviation 10.1 • Interval -2.5 to 2.4	-0.1 mmHg Standard Deviation 11.4 • Interval -1.05 to 2.4
Change From Baseline in Diastolic Blood Pressure Over Time Week 7 (n=54, 52)	1.2 mmHg Standard Deviation 10.4 • Interval -1.2 to 2.9	-1.0 mmHg Standard Deviation 12.3 • Interval -1.75 to 2.57
Change From Baseline in Diastolic Blood Pressure Over Time Week 8 (n=55, 52)	3.9 mmHg Standard Deviation 11.9 • Interval -1.98 to 1.63	1.1 mmHg Standard Deviation 15.0 • Interval -2.71 to 1.17
Change From Baseline in Diastolic Blood Pressure Over Time Week 9 (n=54, 52)	4.8 mmHg Standard Deviation 14.7 • Interval -2.8 to 1.4	-0.3 mmHg Standard Deviation 12.9 • Interval -1.3 to 2.2
Change From Baseline in Diastolic Blood Pressure Over Time Week 10 (n=55, 52)	1.5 mmHg Standard Deviation 13.7 • Interval -1.4 to 3.9	0.9 mmHg Standard Deviation 15.9 • Interval -2.1 to 1.52
Change From Baseline in Diastolic Blood Pressure Over Time Week 13 (n=54, 50)	2.7 mmHg Standard Deviation 13.8 • Interval -2.8 to 2.7	2.2 mmHg Standard Deviation 10.6 • Interval -2.57 to 2.19
Change From Baseline in Diastolic Blood Pressure Over Time Week 14 (n=54, 50)	3.4 mmHg Standard Deviation 14.4 • Interval -1.87 to 2.4	1.7 mmHg Standard Deviation 12.0 • Interval -1.4 to 1.4
Change From Baseline in Diastolic Blood Pressure Over Time Week 15 (n=53, 50)	3.7 mmHg Standard Deviation 12.9 • Interval -1.6 to 2.33	1.4 mmHg Standard Deviation 11.7 • Interval -2.38 to 1.63
Change From Baseline in Diastolic Blood Pressure Over Time Week 16 (n=50, 48)	4.6 mmHg Standard Deviation 13.7 • Interval -2.1 to 3.27	0.7 mmHg Standard Deviation 11.9 • Interval -3.2 to 1.1
Change From Baseline in Diastolic Blood Pressure Over Time Week 17 (n=51, 47)	4.1 mmHg Standard Deviation 15.6 • Interval -2.8 to 2.4	2.6 mmHg Standard Deviation 10.6 • Interval -1.0 to 2.0
Change From Baseline in Diastolic Blood Pressure Over Time Week 18 (n=50, 46)	3.0 mmHg Standard Deviation 16.4 • Interval -2.3 to 1.4	0.4 mmHg Standard Deviation 11.7 • Interval -2.33 to 1.4
Change From Baseline in Diastolic Blood Pressure Over Time Week 19 (n=50, 47)	3.7 mmHg Standard Deviation 12.9 • Interval -1.52 to 1.2	0.6 mmHg Standard Deviation 12.2 • Interval -2.22 to 3.9
Change From Baseline in Diastolic Blood Pressure Over Time Week 20 (n=48, 46)	1.7 mmHg Standard Deviation 13.8 • Interval -1.9 to 2.6	2.0 mmHg Standard Deviation 13.2 • Interval -3.2 to 1.1
Change From Baseline in Diastolic Blood Pressure Over Time Week 21 (n=49, 46)	2.9 mmHg Standard Deviation 15.1 • Interval -1.48 to 2.45	0.6 mmHg Standard Deviation 12.9 • Interval -1.2 to 1.4
Change From Baseline in Diastolic Blood Pressure Over Time Week 22 (n=48, 46)	3.2 mmHg Standard Deviation 14.7 • Interval -2.6 to 1.1	0.3 mmHg Standard Deviation 13.9 • Interval -1.7 to 1.6
Change From Baseline in Diastolic Blood Pressure Over Time Week 23 (n=47, 45)	5.0 mmHg Standard Deviation 13.8 • Interval -2.8 to 1.75	-2.0 mmHg Standard Deviation 14.0 • Interval -1.54 to 1.82
Change From Baseline in Diastolic Blood Pressure Over Time Week 24 (n=46, 46)	4.0 mmHg Standard Deviation 13.8 • Interval -3.03 to 4.34	-0.3 mmHg Standard Deviation 12.8 • Interval -1.6 to 6.44

SECONDARY outcome

Timeframe: 25 weeks

Population: Safety analysis set with both pre and postdose immunoassay antibody results

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.

Outcome measures

Outcome measures
Measure	Darbepoetin Alfa QW n=49 Participants 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.	Darbepoetin Alfa Q2W n=49 Participants 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.
Number of Participants Who Developed Anti-erythropoiesis Antibodies	2 participants	4 participants

SECONDARY outcome

Timeframe: Weeks 1, 2, and 3 before the investigational product dose and 2 days after the first investigational product dose

Population: Due to the low number of participants \<6 years of age summary concentration analyses were not performed.

Serum concentrations of darbepoetin alfa were measured by an enzyme-linked immunosorbent assay (ELISA).

Outcome measures

Outcome data not reported

Adverse Events

Darbepoetin Alfa QW

Serious events: 16 serious events

Other events: 42 other events

Deaths: 0 deaths

Darbepoetin Alfa Q2W

Serious events: 14 serious events

Other events: 43 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Study Director

Amgen Inc.

Phone: 866-572-6436

Results disclosure agreements

Principal investigator is a sponsor employee The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.
Publication restrictions are in place

Restriction type: OTHER

Measure	Darbepoetin Alfa QW n=58 participants at risk 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.	Darbepoetin Alfa Q2W n=56 participants at risk 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.
Blood and lymphatic system disorders Anaemia	1.7% 1/58 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/56 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Blood and lymphatic system disorders Histiocytosis haematophagic	0.00% 0/58 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.8% 1/56 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Cardiac disorders Tachycardia	0.00% 0/58 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.8% 1/56 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Ear and labyrinth disorders Tinnitus	0.00% 0/58 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.8% 1/56 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Abdominal pain	3.4% 2/58 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.8% 1/56 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Vomiting	1.7% 1/58 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/56 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
General disorders Device failure	1.7% 1/58 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/56 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
General disorders Device malfunction	1.7% 1/58 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.8% 1/56 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
General disorders Local swelling	1.7% 1/58 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/56 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
General disorders Medical device complication	1.7% 1/58 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.8% 1/56 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
General disorders Oedema	1.7% 1/58 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/56 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
General disorders Pyrexia	1.7% 1/58 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.8% 1/56 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Appendicitis	1.7% 1/58 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/56 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Bronchitis	0.00% 0/58 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.8% 1/56 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Catheter site infection	1.7% 1/58 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/56 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Cellulitis	1.7% 1/58 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/56 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Clostridium difficile colitis	1.7% 1/58 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/56 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Device related infection	0.00% 0/58 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.8% 1/56 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Device related sepsis	1.7% 1/58 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/56 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Epstein-Barr virus infection	0.00% 0/58 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.8% 1/56 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Escherichia bacteraemia	1.7% 1/58 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/56 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Gastroenteritis clostridial	1.7% 1/58 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/56 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Peritonitis	0.00% 0/58 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	3.6% 2/56 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Peritonitis bacterial	1.7% 1/58 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/56 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Pneumonia	1.7% 1/58 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/56 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Pyelonephritis	1.7% 1/58 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/56 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Sepsis	1.7% 1/58 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/56 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Shunt infection	0.00% 0/58 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.8% 1/56 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Viral infection	1.7% 1/58 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/56 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Injury, poisoning and procedural complications Arteriovenous fistula site complication	1.7% 1/58 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/56 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Injury, poisoning and procedural complications Arteriovenous fistula site haematoma	1.7% 1/58 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/56 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Injury, poisoning and procedural complications Gastrostomy failure	0.00% 0/58 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.8% 1/56 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Injury, poisoning and procedural complications Post procedural haemorrhage	1.7% 1/58 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/56 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Metabolism and nutrition disorders Dehydration	1.7% 1/58 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/56 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Metabolism and nutrition disorders Fluid overload	1.7% 1/58 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/56 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Metabolism and nutrition disorders Hyperkalaemia	5.2% 3/58 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/56 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Metabolism and nutrition disorders Hyperphosphataemia	0.00% 0/58 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.8% 1/56 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Metabolism and nutrition disorders Malnutrition	0.00% 0/58 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.8% 1/56 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Nervous system disorders Headache	3.4% 2/58 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/56 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Nervous system disorders Hypertensive encephalopathy	1.7% 1/58 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/56 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Renal and urinary disorders Renal failure acute	1.7% 1/58 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.8% 1/56 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Renal and urinary disorders Renal failure chronic	0.00% 0/58 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.8% 1/56 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Renal and urinary disorders Renal impairment	3.4% 2/58 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/56 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Renal and urinary disorders Vesical fistula	0.00% 0/58 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.8% 1/56 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Respiratory, thoracic and mediastinal disorders Pulmonary oedema	1.7% 1/58 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.8% 1/56 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Respiratory, thoracic and mediastinal disorders Upper respiratory tract inflammation	0.00% 0/58 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.8% 1/56 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Skin and subcutaneous tissue disorders Decubitus ulcer	0.00% 0/58 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.8% 1/56 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Skin and subcutaneous tissue disorders Swelling face	1.7% 1/58 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/56 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Vascular disorders Hypertension	1.7% 1/58 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	5.4% 3/56 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Vascular disorders Hypertensive crisis	1.7% 1/58 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/56 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Vascular disorders Hypotension	0.00% 0/58 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	3.6% 2/56 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Vascular disorders Orthostatic hypotension	0.00% 0/58 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.8% 1/56 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.

Measure	Darbepoetin Alfa QW n=58 participants at risk 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.	Darbepoetin Alfa Q2W n=56 participants at risk 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.
Gastrointestinal disorders Abdominal pain	10.3% 6/58 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	8.9% 5/56 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Abdominal pain upper	5.2% 3/58 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	3.6% 2/56 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Constipation	6.9% 4/58 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	7.1% 4/56 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Diarrhoea	5.2% 3/58 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	7.1% 4/56 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Nausea	8.6% 5/58 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	7.1% 4/56 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Vomiting	17.2% 10/58 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	16.1% 9/56 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
General disorders Catheter site pain	5.2% 3/58 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.8% 1/56 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
General disorders Fatigue	8.6% 5/58 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	3.6% 2/56 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
General disorders Injection site pain	5.2% 3/58 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	3.6% 2/56 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
General disorders Medical device complication	3.4% 2/58 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	5.4% 3/56 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
General disorders Pyrexia	8.6% 5/58 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	17.9% 10/56 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Catheter site infection	6.9% 4/58 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	5.4% 3/56 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Ear infection	6.9% 4/58 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/56 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Nasopharyngitis	6.9% 4/58 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	10.7% 6/56 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Pharyngitis	3.4% 2/58 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	8.9% 5/56 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Upper respiratory tract infection	5.2% 3/58 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	12.5% 7/56 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Urinary tract infection	6.9% 4/58 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/56 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Injury, poisoning and procedural complications Contusion	1.7% 1/58 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	5.4% 3/56 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Injury, poisoning and procedural complications Procedural hypotension	5.2% 3/58 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	5.4% 3/56 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Investigations Blood pressure increased	5.2% 3/58 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	5.4% 3/56 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Musculoskeletal and connective tissue disorders Back pain	3.4% 2/58 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	5.4% 3/56 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Musculoskeletal and connective tissue disorders Muscle spasms	8.6% 5/58 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	3.6% 2/56 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Musculoskeletal and connective tissue disorders Pain in extremity	6.9% 4/58 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.8% 1/56 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Nervous system disorders Dizziness	5.2% 3/58 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	5.4% 3/56 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Nervous system disorders Headache	6.9% 4/58 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	17.9% 10/56 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Respiratory, thoracic and mediastinal disorders Cough	12.1% 7/58 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	7.1% 4/56 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Respiratory, thoracic and mediastinal disorders Nasal congestion	6.9% 4/58 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.8% 1/56 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	3.4% 2/58 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	5.4% 3/56 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Skin and subcutaneous tissue disorders Pruritus	6.9% 4/58 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.8% 1/56 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Skin and subcutaneous tissue disorders Rash	5.2% 3/58 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.8% 1/56 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Vascular disorders Hypertension	15.5% 9/58 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	14.3% 8/56 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Vascular disorders Hypotension	3.4% 2/58 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	5.4% 3/56 • 25 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.