Trial Outcomes & Findings for Darbepoetin Alfa and Anemia of Cancer (NCT NCT00989092)

Last Updated: 2014-01-29

Results Overview

Number of participants hospitalized during Weeks 1-12 as self-reported in the Health Care Utilization portion of the Subject Outcome Questionaire.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

287 participants

Primary outcome timeframe

Weeks 1- 12

Results posted on

2014-01-29

Participant Flow

First Patient Randomized: 24-Jun-2002 Last Patient Randomized: 08-Aug-2003

Participant milestones

Participant milestones
Measure	Darbepoetin Alfa 3 μg/kg Participants in the treatment group received darbepoetin alfa subcutaneously (SC) at a dose of 3.0 μg/kg once every 2 weeks for 21 weeks. The dose of darbepoetin alfa could be increased at Week 7 (to 5.0 μg/kg once every 2 weeks) or at Week 13 (to 9.0 μg/kg once every 2 weeks) in participants with a hemoglobin change from baseline of less than 1.0 g/dL who dose escalated at Week 7.	Observation Participants in the observation group were evaluated once every 2 weeks for the first 12 weeks (test period). No darbepoetin alfa was administered during this period. Darbepoetin alfa could be initiated at a dose of 3.0 μg/kg once every 2 weeks beginning with the first visit after the test period at which the participant's hemoglobin concentration was less than or equal to 11.0 g/dL. The dose of darbepoetin alfa could be increased to 5.0 μg/kg once every 2 weeks after 6 weeks of darbepoetin alfa treatment in participants with a hemoglobin change from baseline of less than 1.0 g/dL.
Overall Study STARTED	228	59
Overall Study Treated With Darbepoetin Alfa	226	33
Overall Study COMPLETED	138	31
Overall Study NOT COMPLETED	90	28

Reasons for withdrawal

Reasons for withdrawal
Measure	Darbepoetin Alfa 3 μg/kg Participants in the treatment group received darbepoetin alfa subcutaneously (SC) at a dose of 3.0 μg/kg once every 2 weeks for 21 weeks. The dose of darbepoetin alfa could be increased at Week 7 (to 5.0 μg/kg once every 2 weeks) or at Week 13 (to 9.0 μg/kg once every 2 weeks) in participants with a hemoglobin change from baseline of less than 1.0 g/dL who dose escalated at Week 7.	Observation Participants in the observation group were evaluated once every 2 weeks for the first 12 weeks (test period). No darbepoetin alfa was administered during this period. Darbepoetin alfa could be initiated at a dose of 3.0 μg/kg once every 2 weeks beginning with the first visit after the test period at which the participant's hemoglobin concentration was less than or equal to 11.0 g/dL. The dose of darbepoetin alfa could be increased to 5.0 μg/kg once every 2 weeks after 6 weeks of darbepoetin alfa treatment in participants with a hemoglobin change from baseline of less than 1.0 g/dL.
Overall Study Physician Decision	9	6
Overall Study Adverse Event	20	1
Overall Study Chemotherapy initiated	12	4
Overall Study Withdrawal by Subject	17	9
Overall Study Death	14	2
Overall Study Ineligibility determined	3	3
Overall Study Lost to Follow-up	6	2
Overall Study Other	3	1
Overall Study Protocol deviation	2	0
Overall Study Erythropoietin therapy initiated	2	0
Overall Study Did not receive study drug	2	0

Baseline Characteristics

Darbepoetin Alfa and Anemia of Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Darbepoetin Alfa 3 μg/kg n=226 Participants Participants in the treatment group received darbepoetin alfa subcutaneously (SC) at a dose of 3.0 μg/kg once every 2 weeks for 21 weeks. The dose of darbepoetin alfa could be increased at Week 7 (to 5.0 μg/kg once every 2 weeks) or at Week 13 (to 9.0 μg/kg once every 2 weeks) in participants with a hemoglobin change from baseline of less than 1.0 g/dL who dose escalated at Week 7.	Observation n=59 Participants Participants in the observation group were evaluated once every 2 weeks for the first 12 weeks (test period). No darbepoetin alfa was administered during this period. Darbepoetin alfa could be initiated at a dose of 3.0 μg/kg once every 2 weeks beginning with the first visit after the test period at which the participant's hemoglobin concentration was less than or equal to 11.0 g/dL. The dose of darbepoetin alfa could be increased to 5.0 μg/kg once every 2 weeks after 6 weeks of darbepoetin alfa treatment in participants with a hemoglobin change from baseline of less than 1.0 g/dL.	Total n=285 Participants Total of all reporting groups
Age, Continuous	71.7 Years STANDARD_DEVIATION 10.4 • n=5 Participants	67.2 Years STANDARD_DEVIATION 12.5 • n=7 Participants	70.8 Years STANDARD_DEVIATION 11 • n=5 Participants
Sex: Female, Male Female	131 Participants n=5 Participants	36 Participants n=7 Participants	167 Participants n=5 Participants
Sex: Female, Male Male	95 Participants n=5 Participants	23 Participants n=7 Participants	118 Participants n=5 Participants
Race/Ethnicity, Customized White	188 Participant n=5 Participants	46 Participant n=7 Participants	234 Participant n=5 Participants
Race/Ethnicity, Customized Black	28 Participant n=5 Participants	12 Participant n=7 Participants	40 Participant n=5 Participants
Race/Ethnicity, Customized Asian	5 Participant n=5 Participants	1 Participant n=7 Participants	6 Participant n=5 Participants
Race/Ethnicity, Customized Other	5 Participant n=5 Participants	0 Participant n=7 Participants	5 Participant n=5 Participants

PRIMARY outcome

Timeframe: Weeks 1- 12

Population: Includes all randomized patients in the darbepoetin alfa arm who received at least 1 dose of study drug or all randomized patients in the observation arm. Patients also needed to have completed the baseline and at least 1 post-baseline subject outcome questionaire.

Number of participants hospitalized during Weeks 1-12 as self-reported in the Health Care Utilization portion of the Subject Outcome Questionaire.

Outcome measures

Outcome measures
Measure	Darbepoetin Alfa 3 μg/kg n=215 Participants Participants in the treatment group received darbepoetin alfa subcutaneously (SC) at a dose of 3.0 μg/kg once every 2 weeks for 21 weeks. The dose of darbepoetin alfa could be increased at Week 7 (to 5.0 μg/kg once every 2 weeks) or at Week 13 (to 9.0 μg/kg once every 2 weeks) in participants with a hemoglobin change from baseline of less than 1.0 g/dL who dose escalated at Week 7.	Observation n=45 Participants Participants in the observation group were evaluated once every 2 weeks for the first 12 weeks (test period). No darbepoetin alfa was administered during this period. Darbepoetin alfa could be initiated at a dose of 3.0 μg/kg once every 2 weeks beginning with the first visit after the test period at which the participant's hemoglobin concentration was less than or equal to 11.0 g/dL. The dose of darbepoetin alfa could be increased to 5.0 μg/kg once every 2 weeks after 6 weeks of darbepoetin alfa treatment in participants with a hemoglobin change from baseline of less than 1.0 g/dL.
Number of Participants Hospitalized During the Test Period	23 Participants	6 Participants

PRIMARY outcome

Timeframe: Weeks 1-12

Number of days hospitalized during Weeks 1-12 as self-reported in the Health Care Utilization portion of the Subject Outcome Questionaire; participants who were not hospitalized had a value of 0 days.

Outcome measures

Outcome measures
Measure	Darbepoetin Alfa 3 μg/kg n=212 Participants Participants in the treatment group received darbepoetin alfa subcutaneously (SC) at a dose of 3.0 μg/kg once every 2 weeks for 21 weeks. The dose of darbepoetin alfa could be increased at Week 7 (to 5.0 μg/kg once every 2 weeks) or at Week 13 (to 9.0 μg/kg once every 2 weeks) in participants with a hemoglobin change from baseline of less than 1.0 g/dL who dose escalated at Week 7.	Observation n=44 Participants Participants in the observation group were evaluated once every 2 weeks for the first 12 weeks (test period). No darbepoetin alfa was administered during this period. Darbepoetin alfa could be initiated at a dose of 3.0 μg/kg once every 2 weeks beginning with the first visit after the test period at which the participant's hemoglobin concentration was less than or equal to 11.0 g/dL. The dose of darbepoetin alfa could be increased to 5.0 μg/kg once every 2 weeks after 6 weeks of darbepoetin alfa treatment in participants with a hemoglobin change from baseline of less than 1.0 g/dL.
Days of Hospitalization During the Test Period	0.5 days Standard Deviation 2.2	0.5 days Standard Deviation 1.7

PRIMARY outcome

Timeframe: Weeks 1-12

Number of times participants were hospitalized as self-reported in the Health Care Utilization portion of the Subject Outcome Questionaire during Weeks 1-12

Outcome measures

Outcome measures
Measure	Darbepoetin Alfa 3 μg/kg n=215 Participants Participants in the treatment group received darbepoetin alfa subcutaneously (SC) at a dose of 3.0 μg/kg once every 2 weeks for 21 weeks. The dose of darbepoetin alfa could be increased at Week 7 (to 5.0 μg/kg once every 2 weeks) or at Week 13 (to 9.0 μg/kg once every 2 weeks) in participants with a hemoglobin change from baseline of less than 1.0 g/dL who dose escalated at Week 7.	Observation n=45 Participants Participants in the observation group were evaluated once every 2 weeks for the first 12 weeks (test period). No darbepoetin alfa was administered during this period. Darbepoetin alfa could be initiated at a dose of 3.0 μg/kg once every 2 weeks beginning with the first visit after the test period at which the participant's hemoglobin concentration was less than or equal to 11.0 g/dL. The dose of darbepoetin alfa could be increased to 5.0 μg/kg once every 2 weeks after 6 weeks of darbepoetin alfa treatment in participants with a hemoglobin change from baseline of less than 1.0 g/dL.
Number of Hospitalizations During the Test Period	0.1 hospitalizations Standard Deviation 0.5	0.2 hospitalizations Standard Deviation 0.4

SECONDARY outcome

Timeframe: Weeks 1-12

Population: Includes all randomized patients in the darbepoetin alfa arm who received at least 1 dose of study drug or all randomized patients in the observation arm, and were included in the hospital bill database. Participants who were not hospitalized had a cost of $0 imputed.

The hospital bill database was used to determine the mean total hospital cost per participant during the test period. Participants who were not hospitalized had a cost of $0 imputed.

Outcome measures

Outcome measures
Measure	Darbepoetin Alfa 3 μg/kg n=198 Participants Participants in the treatment group received darbepoetin alfa subcutaneously (SC) at a dose of 3.0 μg/kg once every 2 weeks for 21 weeks. The dose of darbepoetin alfa could be increased at Week 7 (to 5.0 μg/kg once every 2 weeks) or at Week 13 (to 9.0 μg/kg once every 2 weeks) in participants with a hemoglobin change from baseline of less than 1.0 g/dL who dose escalated at Week 7.	Observation n=40 Participants Participants in the observation group were evaluated once every 2 weeks for the first 12 weeks (test period). No darbepoetin alfa was administered during this period. Darbepoetin alfa could be initiated at a dose of 3.0 μg/kg once every 2 weeks beginning with the first visit after the test period at which the participant's hemoglobin concentration was less than or equal to 11.0 g/dL. The dose of darbepoetin alfa could be increased to 5.0 μg/kg once every 2 weeks after 6 weeks of darbepoetin alfa treatment in participants with a hemoglobin change from baseline of less than 1.0 g/dL.
Total Hospital Costs During the Test Period	1474.58 dollars Standard Deviation 5528.61	487.31 dollars Standard Deviation 1821.43

SECONDARY outcome

Timeframe: Baseline (Week 1) and Week 13

Population: Includes all randomized patients in the darbepoetin alfa arm who received at least 1 dose of study drug or all randomized patients in the observation arm. Participants also needed to have completed the baseline and at least 1 post-baseline FACT-Fatigue questionaire. Last Value Carried Forward (LVCF) imputation used.

The FACT-Fatigue scale comprises 13 questions evaluating the impact of anemia on cancer patients with various tumor types receiving chemotherapy. Fatigue scores range from 0 to 52, with a higher score indicating less fatigue.

Outcome measures

Outcome measures
Measure	Darbepoetin Alfa 3 μg/kg n=215 Participants Participants in the treatment group received darbepoetin alfa subcutaneously (SC) at a dose of 3.0 μg/kg once every 2 weeks for 21 weeks. The dose of darbepoetin alfa could be increased at Week 7 (to 5.0 μg/kg once every 2 weeks) or at Week 13 (to 9.0 μg/kg once every 2 weeks) in participants with a hemoglobin change from baseline of less than 1.0 g/dL who dose escalated at Week 7.	Observation n=45 Participants Participants in the observation group were evaluated once every 2 weeks for the first 12 weeks (test period). No darbepoetin alfa was administered during this period. Darbepoetin alfa could be initiated at a dose of 3.0 μg/kg once every 2 weeks beginning with the first visit after the test period at which the participant's hemoglobin concentration was less than or equal to 11.0 g/dL. The dose of darbepoetin alfa could be increased to 5.0 μg/kg once every 2 weeks after 6 weeks of darbepoetin alfa treatment in participants with a hemoglobin change from baseline of less than 1.0 g/dL.
Change in Functional Assessment of Cancer Therapy (FACT)-Fatigue Score at Week 13	6.0 units on a scale Standard Deviation 12.0	2.2 units on a scale Standard Deviation 7.6

SECONDARY outcome

Timeframe: Weeks 1-12

Population: Includes all randomized patients in the darbepoetin alfa arm who received at least 1 dose of study drug or all randomized patients in the observation arm. Patients also needed to have a baseline hemoglobin that was not affected by a red blood cell transfusion.

The number of participants achieving a hemoglobin response, defined as an increase in hemoglobin from baseline of ≥ 2.0 g/dL in the absence of red blood cell (RBC) transfusions during the preceding 28 days.

Outcome measures

Outcome measures
Measure	Darbepoetin Alfa 3 μg/kg n=220 Participants Participants in the treatment group received darbepoetin alfa subcutaneously (SC) at a dose of 3.0 μg/kg once every 2 weeks for 21 weeks. The dose of darbepoetin alfa could be increased at Week 7 (to 5.0 μg/kg once every 2 weeks) or at Week 13 (to 9.0 μg/kg once every 2 weeks) in participants with a hemoglobin change from baseline of less than 1.0 g/dL who dose escalated at Week 7.	Observation n=55 Participants Participants in the observation group were evaluated once every 2 weeks for the first 12 weeks (test period). No darbepoetin alfa was administered during this period. Darbepoetin alfa could be initiated at a dose of 3.0 μg/kg once every 2 weeks beginning with the first visit after the test period at which the participant's hemoglobin concentration was less than or equal to 11.0 g/dL. The dose of darbepoetin alfa could be increased to 5.0 μg/kg once every 2 weeks after 6 weeks of darbepoetin alfa treatment in participants with a hemoglobin change from baseline of less than 1.0 g/dL.
Hemoglobin Response During the Test Period	128 Participants	4 Participants

SECONDARY outcome

Timeframe: Weeks 1-12

Population: Includes all randomized patients in the darbepoetin alfa arm who received at least 1 dose of study drug or all randomized patients in the observation arm. Patients also needed to have a baseline hemoglobin that was not affected by a red blood cell transfusion.

The number of participants achieving a hematopoietic response, defined as an increase in hemoglobin from baseline of ≥ 2.0 g/dL or a concentration ≥ 12.0 g/dL both in the absence of red blood cell (RBC) transfusions during the preceding 28 days.

Outcome measures

Outcome measures
Measure	Darbepoetin Alfa 3 μg/kg n=220 Participants Participants in the treatment group received darbepoetin alfa subcutaneously (SC) at a dose of 3.0 μg/kg once every 2 weeks for 21 weeks. The dose of darbepoetin alfa could be increased at Week 7 (to 5.0 μg/kg once every 2 weeks) or at Week 13 (to 9.0 μg/kg once every 2 weeks) in participants with a hemoglobin change from baseline of less than 1.0 g/dL who dose escalated at Week 7.	Observation n=55 Participants Participants in the observation group were evaluated once every 2 weeks for the first 12 weeks (test period). No darbepoetin alfa was administered during this period. Darbepoetin alfa could be initiated at a dose of 3.0 μg/kg once every 2 weeks beginning with the first visit after the test period at which the participant's hemoglobin concentration was less than or equal to 11.0 g/dL. The dose of darbepoetin alfa could be increased to 5.0 μg/kg once every 2 weeks after 6 weeks of darbepoetin alfa treatment in participants with a hemoglobin change from baseline of less than 1.0 g/dL.
Hematopoietic Response During the Test Period	145 Participants	10 Participants

SECONDARY outcome

Timeframe: Baseline (Week 1) and Week 13

Population: Includes all randomized patients in the darbepoetin alfa arm who received at least 1 dose of study drug or all randomized patients in the observation arm. Patients also needed to have a baseline hemoglobin that was not affected by a red blood cell transfusion. LVCF imputation was used.

The difference between hemoglobin concentrations after 12 weeks of treatment and the Baseline hemoglobin concentration value (Study Day 1 sample prior to first dose of darbepoetin alfa).

Outcome measures

Outcome measures
Measure	Darbepoetin Alfa 3 μg/kg n=220 Participants Participants in the treatment group received darbepoetin alfa subcutaneously (SC) at a dose of 3.0 μg/kg once every 2 weeks for 21 weeks. The dose of darbepoetin alfa could be increased at Week 7 (to 5.0 μg/kg once every 2 weeks) or at Week 13 (to 9.0 μg/kg once every 2 weeks) in participants with a hemoglobin change from baseline of less than 1.0 g/dL who dose escalated at Week 7.	Observation n=55 Participants Participants in the observation group were evaluated once every 2 weeks for the first 12 weeks (test period). No darbepoetin alfa was administered during this period. Darbepoetin alfa could be initiated at a dose of 3.0 μg/kg once every 2 weeks beginning with the first visit after the test period at which the participant's hemoglobin concentration was less than or equal to 11.0 g/dL. The dose of darbepoetin alfa could be increased to 5.0 μg/kg once every 2 weeks after 6 weeks of darbepoetin alfa treatment in participants with a hemoglobin change from baseline of less than 1.0 g/dL.
Change From Baseline in Hemoglobin Level	2.1 g/dL Standard Deviation 1.9	0.1 g/dL Standard Deviation 0.8

SECONDARY outcome

Timeframe: Weeks 1-12

Population: Includes all randomized patients in the darbepoetin alfa arm who received at least 1 dose of study drug or all randomized patients in the observation arm with available data.

Number of participants with at least one RBC transfusion during Weeks 1 to 12.

Outcome measures

Outcome measures
Measure	Darbepoetin Alfa 3 μg/kg n=226 Participants Participants in the treatment group received darbepoetin alfa subcutaneously (SC) at a dose of 3.0 μg/kg once every 2 weeks for 21 weeks. The dose of darbepoetin alfa could be increased at Week 7 (to 5.0 μg/kg once every 2 weeks) or at Week 13 (to 9.0 μg/kg once every 2 weeks) in participants with a hemoglobin change from baseline of less than 1.0 g/dL who dose escalated at Week 7.	Observation n=59 Participants Participants in the observation group were evaluated once every 2 weeks for the first 12 weeks (test period). No darbepoetin alfa was administered during this period. Darbepoetin alfa could be initiated at a dose of 3.0 μg/kg once every 2 weeks beginning with the first visit after the test period at which the participant's hemoglobin concentration was less than or equal to 11.0 g/dL. The dose of darbepoetin alfa could be increased to 5.0 μg/kg once every 2 weeks after 6 weeks of darbepoetin alfa treatment in participants with a hemoglobin change from baseline of less than 1.0 g/dL.
Number of Participants With Red Blood Cell (RBC) Transfusions During the Test Period	25 Participants	11 Participants

SECONDARY outcome

Timeframe: Weeks 1-12

Population: Includes all randomized patients in the darbepoetin alfa arm who received at least 1 dose of study drug or all randomized patients in the observation arm.

The average number of standard units of red blood cells transfused during Weeks 1 to 12.

Outcome measures

Outcome measures
Measure	Darbepoetin Alfa 3 μg/kg n=226 Participants Participants in the treatment group received darbepoetin alfa subcutaneously (SC) at a dose of 3.0 μg/kg once every 2 weeks for 21 weeks. The dose of darbepoetin alfa could be increased at Week 7 (to 5.0 μg/kg once every 2 weeks) or at Week 13 (to 9.0 μg/kg once every 2 weeks) in participants with a hemoglobin change from baseline of less than 1.0 g/dL who dose escalated at Week 7.	Observation n=59 Participants Participants in the observation group were evaluated once every 2 weeks for the first 12 weeks (test period). No darbepoetin alfa was administered during this period. Darbepoetin alfa could be initiated at a dose of 3.0 μg/kg once every 2 weeks beginning with the first visit after the test period at which the participant's hemoglobin concentration was less than or equal to 11.0 g/dL. The dose of darbepoetin alfa could be increased to 5.0 μg/kg once every 2 weeks after 6 weeks of darbepoetin alfa treatment in participants with a hemoglobin change from baseline of less than 1.0 g/dL.
Number of Units of Red Blood Cells Transfused During the Test Period	0.4 units of red blood cells Standard Deviation 1.4	0.9 units of red blood cells Standard Deviation 2.4

SECONDARY outcome

Timeframe: Weeks 1-12

Population: Includes all randomized patients in the darbepoetin alfa arm who received at least 1 dose of study drug or all randomized patients in the observation arm.

The number of days when at least one red blood cell transfusion was administered during Weeks 1 to 12.

Outcome measures

Outcome measures
Measure	Darbepoetin Alfa 3 μg/kg n=226 Participants Participants in the treatment group received darbepoetin alfa subcutaneously (SC) at a dose of 3.0 μg/kg once every 2 weeks for 21 weeks. The dose of darbepoetin alfa could be increased at Week 7 (to 5.0 μg/kg once every 2 weeks) or at Week 13 (to 9.0 μg/kg once every 2 weeks) in participants with a hemoglobin change from baseline of less than 1.0 g/dL who dose escalated at Week 7.	Observation n=59 Participants Participants in the observation group were evaluated once every 2 weeks for the first 12 weeks (test period). No darbepoetin alfa was administered during this period. Darbepoetin alfa could be initiated at a dose of 3.0 μg/kg once every 2 weeks beginning with the first visit after the test period at which the participant's hemoglobin concentration was less than or equal to 11.0 g/dL. The dose of darbepoetin alfa could be increased to 5.0 μg/kg once every 2 weeks after 6 weeks of darbepoetin alfa treatment in participants with a hemoglobin change from baseline of less than 1.0 g/dL.
Number of Days of Red Blood Cell Transfusions During the Test Period	0.2 days Standard Deviation 0.6	0.4 days Standard Deviation 1.0

SECONDARY outcome

Timeframe: Weeks 5-12

Population: Includes all randomized patients in the darbepoetin alfa arm who received at least 1 dose of study drug or all randomized patients in the observation arm, and who were on-study as of the beginning of Week 5 (Study Day 29).

The number of participants with at least one RBC transfusion during weeks 5 to 12.

Outcome measures

Outcome measures
Measure	Darbepoetin Alfa 3 μg/kg n=215 Participants Participants in the treatment group received darbepoetin alfa subcutaneously (SC) at a dose of 3.0 μg/kg once every 2 weeks for 21 weeks. The dose of darbepoetin alfa could be increased at Week 7 (to 5.0 μg/kg once every 2 weeks) or at Week 13 (to 9.0 μg/kg once every 2 weeks) in participants with a hemoglobin change from baseline of less than 1.0 g/dL who dose escalated at Week 7.	Observation n=47 Participants Participants in the observation group were evaluated once every 2 weeks for the first 12 weeks (test period). No darbepoetin alfa was administered during this period. Darbepoetin alfa could be initiated at a dose of 3.0 μg/kg once every 2 weeks beginning with the first visit after the test period at which the participant's hemoglobin concentration was less than or equal to 11.0 g/dL. The dose of darbepoetin alfa could be increased to 5.0 μg/kg once every 2 weeks after 6 weeks of darbepoetin alfa treatment in participants with a hemoglobin change from baseline of less than 1.0 g/dL.
Number of Participants With Red Blood Cell (RBC) Transfusions During Weeks 5-12	16 Participants	10 Participants

SECONDARY outcome

Timeframe: Weeks 5-12

The number of standard units of RBCs transfused during Weeks 5 to 12.

Outcome measures

Outcome measures
Measure	Darbepoetin Alfa 3 μg/kg n=215 Participants Participants in the treatment group received darbepoetin alfa subcutaneously (SC) at a dose of 3.0 μg/kg once every 2 weeks for 21 weeks. The dose of darbepoetin alfa could be increased at Week 7 (to 5.0 μg/kg once every 2 weeks) or at Week 13 (to 9.0 μg/kg once every 2 weeks) in participants with a hemoglobin change from baseline of less than 1.0 g/dL who dose escalated at Week 7.	Observation n=47 Participants Participants in the observation group were evaluated once every 2 weeks for the first 12 weeks (test period). No darbepoetin alfa was administered during this period. Darbepoetin alfa could be initiated at a dose of 3.0 μg/kg once every 2 weeks beginning with the first visit after the test period at which the participant's hemoglobin concentration was less than or equal to 11.0 g/dL. The dose of darbepoetin alfa could be increased to 5.0 μg/kg once every 2 weeks after 6 weeks of darbepoetin alfa treatment in participants with a hemoglobin change from baseline of less than 1.0 g/dL.
Number of Units of Red Blood Cells Transfused During Weeks 5-12	0.2 units of red blood cells Standard Deviation 1.0	0.8 units of red blood cells Standard Deviation 1.8

SECONDARY outcome

Timeframe: Weeks 5-12

The number of days when at least one RBC transfusion was administered during Weeks 5 to 12.

Outcome measures

Outcome measures
Measure	Darbepoetin Alfa 3 μg/kg n=215 Participants Participants in the treatment group received darbepoetin alfa subcutaneously (SC) at a dose of 3.0 μg/kg once every 2 weeks for 21 weeks. The dose of darbepoetin alfa could be increased at Week 7 (to 5.0 μg/kg once every 2 weeks) or at Week 13 (to 9.0 μg/kg once every 2 weeks) in participants with a hemoglobin change from baseline of less than 1.0 g/dL who dose escalated at Week 7.	Observation n=47 Participants Participants in the observation group were evaluated once every 2 weeks for the first 12 weeks (test period). No darbepoetin alfa was administered during this period. Darbepoetin alfa could be initiated at a dose of 3.0 μg/kg once every 2 weeks beginning with the first visit after the test period at which the participant's hemoglobin concentration was less than or equal to 11.0 g/dL. The dose of darbepoetin alfa could be increased to 5.0 μg/kg once every 2 weeks after 6 weeks of darbepoetin alfa treatment in participants with a hemoglobin change from baseline of less than 1.0 g/dL.
Number of Days of Red Blood Cell Transfusions During Weeks 5-12	0.1 days Standard Deviation 0.5	0.4 days Standard Deviation 0.8

Adverse Events

Treatment Arm

Serious events: 65 serious events

Other events: 99 other events

Deaths: 0 deaths

Observation Arm Treated

Serious events: 4 serious events

Other events: 21 other events

Deaths: 0 deaths

Observation Arm Not Treated

Serious events: 4 serious events

Other events: 6 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 multi-center studies, the investigator agrees not to publish any results before the first multi-center publication.
Publication restrictions are in place

Restriction type: OTHER

Measure	Treatment Arm n=226 participants at risk Participants in the treatment group received darbepoetin alfa subcutaneously (SC) at a dose of 3.0 μg/kg once every 2 weeks for 21 weeks. The dose of darbepoetin alfa could be increased at week 7 (to 5.0 μg/kg once every 2 weeks) or at week 13 (to 9.0 μg/kg once every 2 weeks) in participants with a hemoglobin change from baseline of less than 1.0 g/dL who dose escalated at week 7.	Observation Arm Treated n=33 participants at risk Participants in the observation group who received darbepoetin alfa, initiated at a dose of 3.0 μg/kg once every 2 weeks beginning with the first visit after the test period at which the participants hemoglobin concentration was less than or equal to 11.0 g/dL. The dose of darbepoetin alfa could be increased to 5.0 μg/kg once every 2 weeks after 6 weeks of darbepoetin alfa treatment in participants with a hemoglobin change from baseline of less than 1.0 g/dL. Adverse events for participants in this group could have been reported at any time during the study; and therefore, may have occurred before darbepoetin alfa administration.	Observation Arm Not Treated n=26 participants at risk Participants in the observation group who did not receive any darbepoetin alfa treatment.
Gastrointestinal disorders Abdominal pain	0.88% 2/226 • First dose through End of Study or 30 days after last dose, up to 25 weeks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	6.1% 2/33 • First dose through End of Study or 30 days after last dose, up to 25 weeks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/26 • First dose through End of Study or 30 days after last dose, up to 25 weeks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Gastrointestinal disorders Constipation	5.8% 13/226 • First dose through End of Study or 30 days after last dose, up to 25 weeks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	3.0% 1/33 • First dose through End of Study or 30 days after last dose, up to 25 weeks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	3.8% 1/26 • First dose through End of Study or 30 days after last dose, up to 25 weeks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Gastrointestinal disorders Diarrhoea	7.1% 16/226 • First dose through End of Study or 30 days after last dose, up to 25 weeks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	12.1% 4/33 • First dose through End of Study or 30 days after last dose, up to 25 weeks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	3.8% 1/26 • First dose through End of Study or 30 days after last dose, up to 25 weeks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Gastrointestinal disorders Dyspepsia	1.8% 4/226 • First dose through End of Study or 30 days after last dose, up to 25 weeks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	6.1% 2/33 • First dose through End of Study or 30 days after last dose, up to 25 weeks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/26 • First dose through End of Study or 30 days after last dose, up to 25 weeks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Gastrointestinal disorders Gastrooesophageal reflux disease	0.88% 2/226 • First dose through End of Study or 30 days after last dose, up to 25 weeks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	6.1% 2/33 • First dose through End of Study or 30 days after last dose, up to 25 weeks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/26 • First dose through End of Study or 30 days after last dose, up to 25 weeks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Gastrointestinal disorders Haemorrhoids	0.88% 2/226 • First dose through End of Study or 30 days after last dose, up to 25 weeks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	6.1% 2/33 • First dose through End of Study or 30 days after last dose, up to 25 weeks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/26 • First dose through End of Study or 30 days after last dose, up to 25 weeks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Gastrointestinal disorders Nausea	2.2% 5/226 • First dose through End of Study or 30 days after last dose, up to 25 weeks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	6.1% 2/33 • First dose through End of Study or 30 days after last dose, up to 25 weeks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/26 • First dose through End of Study or 30 days after last dose, up to 25 weeks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Gastrointestinal disorders Rectal haemorrhage	0.88% 2/226 • First dose through End of Study or 30 days after last dose, up to 25 weeks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	6.1% 2/33 • First dose through End of Study or 30 days after last dose, up to 25 weeks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/26 • First dose through End of Study or 30 days after last dose, up to 25 weeks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
General disorders Asthenia	9.7% 22/226 • First dose through End of Study or 30 days after last dose, up to 25 weeks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	6.1% 2/33 • First dose through End of Study or 30 days after last dose, up to 25 weeks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	7.7% 2/26 • First dose through End of Study or 30 days after last dose, up to 25 weeks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
General disorders Fatigue	18.6% 42/226 • First dose through End of Study or 30 days after last dose, up to 25 weeks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	18.2% 6/33 • First dose through End of Study or 30 days after last dose, up to 25 weeks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	11.5% 3/26 • First dose through End of Study or 30 days after last dose, up to 25 weeks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
General disorders Oedema peripheral	8.8% 20/226 • First dose through End of Study or 30 days after last dose, up to 25 weeks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	3.0% 1/33 • First dose through End of Study or 30 days after last dose, up to 25 weeks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	3.8% 1/26 • First dose through End of Study or 30 days after last dose, up to 25 weeks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
General disorders Pain	4.0% 9/226 • First dose through End of Study or 30 days after last dose, up to 25 weeks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	6.1% 2/33 • First dose through End of Study or 30 days after last dose, up to 25 weeks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	3.8% 1/26 • First dose through End of Study or 30 days after last dose, up to 25 weeks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Infections and infestations Nasopharyngitis	0.88% 2/226 • First dose through End of Study or 30 days after last dose, up to 25 weeks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	6.1% 2/33 • First dose through End of Study or 30 days after last dose, up to 25 weeks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/26 • First dose through End of Study or 30 days after last dose, up to 25 weeks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Musculoskeletal and connective tissue disorders Arthralgia	7.5% 17/226 • First dose through End of Study or 30 days after last dose, up to 25 weeks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	12.1% 4/33 • First dose through End of Study or 30 days after last dose, up to 25 weeks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	3.8% 1/26 • First dose through End of Study or 30 days after last dose, up to 25 weeks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Musculoskeletal and connective tissue disorders Arthritis	0.88% 2/226 • First dose through End of Study or 30 days after last dose, up to 25 weeks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	6.1% 2/33 • First dose through End of Study or 30 days after last dose, up to 25 weeks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/26 • First dose through End of Study or 30 days after last dose, up to 25 weeks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Musculoskeletal and connective tissue disorders Back pain	3.5% 8/226 • First dose through End of Study or 30 days after last dose, up to 25 weeks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	15.2% 5/33 • First dose through End of Study or 30 days after last dose, up to 25 weeks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	3.8% 1/26 • First dose through End of Study or 30 days after last dose, up to 25 weeks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Musculoskeletal and connective tissue disorders Neck pain	2.2% 5/226 • First dose through End of Study or 30 days after last dose, up to 25 weeks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	6.1% 2/33 • First dose through End of Study or 30 days after last dose, up to 25 weeks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/26 • First dose through End of Study or 30 days after last dose, up to 25 weeks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Nervous system disorders Dizziness	5.3% 12/226 • First dose through End of Study or 30 days after last dose, up to 25 weeks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	9.1% 3/33 • First dose through End of Study or 30 days after last dose, up to 25 weeks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	3.8% 1/26 • First dose through End of Study or 30 days after last dose, up to 25 weeks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Nervous system disorders Hypoaesthesia	0.44% 1/226 • First dose through End of Study or 30 days after last dose, up to 25 weeks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	6.1% 2/33 • First dose through End of Study or 30 days after last dose, up to 25 weeks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/26 • First dose through End of Study or 30 days after last dose, up to 25 weeks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Respiratory, thoracic and mediastinal disorders Cough	4.9% 11/226 • First dose through End of Study or 30 days after last dose, up to 25 weeks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	9.1% 3/33 • First dose through End of Study or 30 days after last dose, up to 25 weeks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/26 • First dose through End of Study or 30 days after last dose, up to 25 weeks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Respiratory, thoracic and mediastinal disorders Dyspnoea	9.3% 21/226 • First dose through End of Study or 30 days after last dose, up to 25 weeks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	18.2% 6/33 • First dose through End of Study or 30 days after last dose, up to 25 weeks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	7.7% 2/26 • First dose through End of Study or 30 days after last dose, up to 25 weeks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	1.3% 3/226 • First dose through End of Study or 30 days after last dose, up to 25 weeks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	6.1% 2/33 • First dose through End of Study or 30 days after last dose, up to 25 weeks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/26 • First dose through End of Study or 30 days after last dose, up to 25 weeks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Respiratory, thoracic and mediastinal disorders Pharyngolaryngeal pain	3.1% 7/226 • First dose through End of Study or 30 days after last dose, up to 25 weeks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	6.1% 2/33 • First dose through End of Study or 30 days after last dose, up to 25 weeks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/26 • First dose through End of Study or 30 days after last dose, up to 25 weeks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/226 • First dose through End of Study or 30 days after last dose, up to 25 weeks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	6.1% 2/33 • First dose through End of Study or 30 days after last dose, up to 25 weeks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/26 • First dose through End of Study or 30 days after last dose, up to 25 weeks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Vascular disorders Hot flush	0.88% 2/226 • First dose through End of Study or 30 days after last dose, up to 25 weeks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	6.1% 2/33 • First dose through End of Study or 30 days after last dose, up to 25 weeks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/26 • First dose through End of Study or 30 days after last dose, up to 25 weeks. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.