Trial Outcomes & Findings for Darbepoetin Alfa in Patients With Anemic Low or Intermediate-1 Risk Myelodysplastic Syndrome (MDS) (NCT NCT01362140)

NCT ID: NCT01362140

Last Updated: 2017-12-19

Results Overview

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

147 participants

Primary outcome timeframe

Week 5 to Week 25

Results posted on

2017-12-19

Participant Flow

This study was conducted at 49 centers in 9 countries. Participants were enrolled from 21 December 2011 to 06 January 2014. Results are reported for the double-blind treatment period of the study, with a 07 October 2015 data cut-off; the study is ongoing.

Eligible participants were randomized in a 2:1 ratio to receive darbepoetin alfa or placebo. Randomization was stratified by International Prognostic Scoring System (IPSS) category (low vs intermediate-1 risk) established at screening.

Participant milestones

Participant milestones
Measure	Placebo Participants received placebo subcutaneous injection every 3 weeks (Q3W) for 24 weeks.	Darbepoetin Alfa Participants received darbepoetin alfa 500 µg Q3W for 24 weeks.
Overall Study STARTED	49	98
Overall Study Received Treatment	49	97
Overall Study COMPLETED	39	87
Overall Study NOT COMPLETED	10	11

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Participants received placebo subcutaneous injection every 3 weeks (Q3W) for 24 weeks.	Darbepoetin Alfa Participants received darbepoetin alfa 500 µg Q3W for 24 weeks.
Overall Study Noncompliance	1	0
Overall Study Adverse Event	2	2
Overall Study Withdrawal by Subject	3	3
Overall Study Administrative Decision	0	1
Overall Study Death	2	1
Overall Study Other	1	1
Overall Study Protocol-specified Criteria	1	2
Overall Study Discontinued Without Receiving Treatment	0	1

Baseline Characteristics

Darbepoetin Alfa in Patients With Anemic Low or Intermediate-1 Risk Myelodysplastic Syndrome (MDS)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=49 Participants Participants received placebo subcutaneous injection every 3 weeks (Q3W) for 24 weeks.	Darbepoetin Alfa n=97 Participants Participants received darbepoetin alfa 500 µg Q3W for 24 weeks.	Total n=146 Participants Total of all reporting groups
Age, Continuous	72.4 years STANDARD_DEVIATION 9.3 • n=5 Participants	72.4 years STANDARD_DEVIATION 9.4 • n=7 Participants	72.4 years STANDARD_DEVIATION 9.4 • n=5 Participants
Sex: Female, Male Female	20 Participants n=5 Participants	46 Participants n=7 Participants	66 Participants n=5 Participants
Sex: Female, Male Male	29 Participants n=5 Participants	51 Participants n=7 Participants	80 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	45 Participants n=5 Participants	90 Participants n=7 Participants	135 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants	5 Participants n=7 Participants	8 Participants n=5 Participants
Race/Ethnicity, Customized White	49 participants n=5 Participants	97 participants n=7 Participants	146 participants n=5 Participants
IPSS Risk Category Low	25 participants n=5 Participants	49 participants n=7 Participants	74 participants n=5 Participants
IPSS Risk Category Intermediate-1	24 participants n=5 Participants	48 participants n=7 Participants	72 participants n=5 Participants
World Health Organization (WHO) Classification of MDS Refractory anemia (RA)	13 participants n=5 Participants	9 participants n=7 Participants	22 participants n=5 Participants
World Health Organization (WHO) Classification of MDS RA with ringed sideroblasts (RARS)	4 participants n=5 Participants	17 participants n=7 Participants	21 participants n=5 Participants
World Health Organization (WHO) Classification of MDS Refractory cytopenia multilineage dysplasia (RCMD)	19 participants n=5 Participants	45 participants n=7 Participants	64 participants n=5 Participants
World Health Organization (WHO) Classification of MDS MDS, unclassified (MDS-U)	1 participants n=5 Participants	1 participants n=7 Participants	2 participants n=5 Participants
World Health Organization (WHO) Classification of MDS MDS associated with isolated del(5q)	2 participants n=5 Participants	11 participants n=7 Participants	13 participants n=5 Participants
World Health Organization (WHO) Classification of MDS Refractory anemia with excess blasts-1 (RAEB-1)	10 participants n=5 Participants	13 participants n=7 Participants	23 participants n=5 Participants
World Health Organization (WHO) Classification of MDS Refractory anemia with excess blasts-2 (RAEB-2)	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants
World Health Organization (WHO) Classification of MDS Unknown	0 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants
Time since MDS Diagnosis	11.7 months STANDARD_DEVIATION 17.6 • n=5 Participants	12.4 months STANDARD_DEVIATION 16.7 • n=7 Participants	12.2 months STANDARD_DEVIATION 16.9 • n=5 Participants
Hemoglobin	9.10 g/dL STANDARD_DEVIATION 0.87 • n=5 Participants	9.23 g/dL STANDARD_DEVIATION 0.70 • n=7 Participants	9.19 g/dL STANDARD_DEVIATION 0.76 • n=5 Participants

PRIMARY outcome

Timeframe: Week 5 to Week 25

Population: Transfusion Primary Analysis Set which includes all randomized and consented participants who received at least 1 dose of study drug and who had an end of treatment period (EOTP) visit ≥ day 29 (ie, start of week 5).

Outcome measures

Outcome measures
Measure	Placebo n=49 Participants Participants received placebo subcutaneous injection every 3 weeks (Q3W) for 24 weeks.	Darbepoetin Alfa n=97 Participants Participants received darbepoetin alfa 500 µg Q3W for 24 weeks.
Percentage of Participants With at Least One Red Blood Cell (RBC) Transfusion During the Double-blind Treatment Period	59.2 percentage of participants	36.1 percentage of participants

SECONDARY outcome

Timeframe: Up to 24 weeks

Population: Primary analysis set participants with a central laboratory baseline hemoglobin value

International Working Group 2006 erythroid response was defined as achieving an initial ≥ 1.5 g/dL increase in hemoglobin from baseline and sustaining an average rise of ≥ 1.5 g/dL in a rolling 56-consecutive day period in the absence of RBC transfusion. Participants with no hemoglobin collected to the minimum time required to observe an IWG erythroid response (Week 13) were considered non-responders.

Outcome measures

Outcome measures
Measure	Placebo n=35 Participants Participants received placebo subcutaneous injection every 3 weeks (Q3W) for 24 weeks.	Darbepoetin Alfa n=75 Participants Participants received darbepoetin alfa 500 µg Q3W for 24 weeks.
Percentage of Participants Who Achieved an Erythroid Response Based on International Working Group (IWG) 2006 Criteria in the Double-blind Treatment Period	0.0 percentage of participants Interval 0.0 to 10.0	14.7 percentage of participants Interval 7.56 to 24.73

SECONDARY outcome

Timeframe: From first dose of study drug until the end of the double-blind treatment period; 24 weeks.

Population: Safety Analysis Set, including all participants who received at least 1 dose of study drug. One participant in the placebo arm inadvertently received a dose of darbepoetin alfa and is counted in the darbepoetin alfa group for safety analyses.

The severity of each adverse event was graded using the the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 grading scale, where grade 1 = mild, grade 2 = moderate, grade 3 = severe, grade 4 = life-threatening and grade 5 = death. Prespecified adverse events of interest for darbepoetin alfa, based on clinical data in anemic patients with cancer, included the following categories: hypersensitivity, cardiac failure, hypertension, malignancies, embolic and thrombolic events, venous thromboembolic events (VTEs), central nervous system vascular disorders, and ischemic heart disease.

Outcome measures

Outcome measures
Measure	Placebo n=48 Participants Participants received placebo subcutaneous injection every 3 weeks (Q3W) for 24 weeks.	Darbepoetin Alfa n=98 Participants Participants received darbepoetin alfa 500 µg Q3W for 24 weeks.
Number of Participants With Adverse Events Any adverse event (AE)	37 participants	80 participants
Number of Participants With Adverse Events AE Grade ≥ 2	23 participants	42 participants
Number of Participants With Adverse Events AE Grade ≥ 3	13 participants	15 participants
Number of Participants With Adverse Events AE Grade ≥ 4	6 participants	5 participants
Number of Participants With Adverse Events Serious adverse events (SAE)	8 participants	11 participants
Number of Participants With Adverse Events AE leading to discontinuation of study drug	2 participants	3 participants
Number of Participants With Adverse Events Fatal adverse events	2 participants	1 participants
Number of Participants With Adverse Events Adverse events of special interest	13 participants	16 participants
Number of Participants With Adverse Events Treatment-related adverse events (TRAE)	4 participants	5 participants
Number of Participants With Adverse Events Treatment-related serious adverse events	0 participants	1 participants
Number of Participants With Adverse Events TRAE leading to discontinuation of study drug	0 participants	1 participants
Number of Participants With Adverse Events Treatment-related fatal adverse events	0 participants	0 participants

SECONDARY outcome

Timeframe: 24 weeks

Population: Safety analysis set with available data

Transformation to AML was assessed according to WHO guidelines in the absence of IP and any haematopoietic growth factors (2 weeks off dosing). Bone marrow and/or cytogenetic report confirmation of AML was required (marrow or peripheral blast cells ≥ 20%, presence of pathognomic AML cytogenetic change, or evidence of marrow blast criteria for erythroleukemia). A pathology report confirming other leukemias such as chloroma (granulocytic sarcoma, myeloid sarcoma) or leukemia cutis also constituted transformation to AML.

Outcome measures

Outcome measures
Measure	Placebo n=46 Participants Participants received placebo subcutaneous injection every 3 weeks (Q3W) for 24 weeks.	Darbepoetin Alfa n=95 Participants Participants received darbepoetin alfa 500 µg Q3W for 24 weeks.
Number of Participants With Disease Progression to Acute Myeloid Leukemia (AML)	1 participants	2 participants

SECONDARY outcome

Timeframe: Up to 24 weeks

Population: Safety analysis set

Outcome measures

Outcome measures
Measure	Placebo n=48 Participants Participants received placebo subcutaneous injection every 3 weeks (Q3W) for 24 weeks.	Darbepoetin Alfa n=98 Participants Participants received darbepoetin alfa 500 µg Q3W for 24 weeks.
Number of Participants With Malignancies Other Than AML, Basal Cell Carcinoma, or Squamous Cell Carcinoma of the Skin	0 participants	1 participants

SECONDARY outcome

Timeframe: Baseline and end of double-blind treatment period (24 weeks)

Population: Safety analysis set participants with post-baseline antibody results

Two validated assays were used to detect the presence of anti-darbepoetin alfa antibodies. Samples were first tested in an immunoassay to detect antibodies capable of binding to darbepoetin alfa. Samples confirmed to be positive for binding antibodies were subsequently tested in a cell-based assay to determine neutralizing activity against darbepoetin alfa. If a sample was positive for binding antibodies and demonstrated neutralizing activity at the same time point, the sample was defined as positive for neutralizing antibodies. The number of participants who developed antibodies to darbepoetin alfa is defined as participants who were neutralizing antibody positive post-baseline with a negative or no result at baseline.

Outcome measures

Outcome measures
Measure	Placebo n=43 Participants Participants received placebo subcutaneous injection every 3 weeks (Q3W) for 24 weeks.	Darbepoetin Alfa n=91 Participants Participants received darbepoetin alfa 500 µg Q3W for 24 weeks.
Number of Participants Who Developed Neutralizing Antibodies to Darbepoetin Alfa	0 participants	0 participants

SECONDARY outcome

Timeframe: Baseline, and weeks 13 and 25

Population: FACIT-Fatigue Analysis Set, includes all participants in the primary analysis set who completed or partially completed both the baseline and at least 1 subsequent FACIT-F questionnaire.

The FACIT-Fatigue scale was a 13-item self-administered questionnaire that assesses both the physical and functional consequences of fatigue. Each question is answered on a 5-point scale, where 0 means "not at all," and 4 means "very much." The FACIT-Fatigue scale score ranges from 0 to 52, with higher scores denoting lower levels of fatigue. A positive change from baseline score indicates an improvement. End of treatment period (EOTP) analysis includes last available values.

Outcome measures

Outcome measures
Measure	Placebo n=42 Participants Participants received placebo subcutaneous injection every 3 weeks (Q3W) for 24 weeks.	Darbepoetin Alfa n=90 Participants Participants received darbepoetin alfa 500 µg Q3W for 24 weeks.
Change From Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Baseline (N = 42, 90)	32.9 units on a scale Standard Deviation 11.4	33.1 units on a scale Standard Deviation 11.4
Change From Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Change from Baseline to Week 13 (n = 41, 85)	-0.9 units on a scale Standard Deviation 9.0	2.7 units on a scale Standard Deviation 7.2
Change From Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Change from Baseline to Week 25 (n = 39, 85)	0.6 units on a scale Standard Deviation 5.5	1.2 units on a scale Standard Deviation 8.9
Change From Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Change from Baseline to EOTP (n = 42, 90)	-0.5 units on a scale Standard Deviation 7.1	1.1 units on a scale Standard Deviation 8.8

SECONDARY outcome

Timeframe: Baseline, and weeks 13 and 25

Population: The EQ-5D visual analog analysis set includes all participants in the primary analysis set who completed both the baseline and at least 1 subsequent visual analog scale.

The EQ-5D visual analog scale (VAS) is a global evaluation of overall health state with scores ranging from 0 (worse health state a participant can imagine) to 100 (best health state a participant can imagine). End of treatment period (EOTP) analysis includes last available values.

Outcome measures

Outcome measures
Measure	Placebo n=42 Participants Participants received placebo subcutaneous injection every 3 weeks (Q3W) for 24 weeks.	Darbepoetin Alfa n=90 Participants Participants received darbepoetin alfa 500 µg Q3W for 24 weeks.
Change From Baseline in EuroQol-5D (EQ-5D) Visual Analog Scale (VAS) Baseline (N = 42, 90)	64.4 units on a scale Standard Deviation 17.9	64.8 units on a scale Standard Deviation 17.2
Change From Baseline in EuroQol-5D (EQ-5D) Visual Analog Scale (VAS) Change from Baseline to Week 13 (n = 41, 83)	-1.9 units on a scale Standard Deviation 15.5	2.9 units on a scale Standard Deviation 13.0
Change From Baseline in EuroQol-5D (EQ-5D) Visual Analog Scale (VAS) Change from Baseline to Week 25 (n = 39, 81)	2.1 units on a scale Standard Deviation 15.3	2.4 units on a scale Standard Deviation 13.5
Change From Baseline in EuroQol-5D (EQ-5D) Visual Analog Scale (VAS) Change from Baseline to EOTP (n = 42, 89)	0.8 units on a scale Standard Deviation 15.7	2.1 units on a scale Standard Deviation 13.1

SECONDARY outcome

Timeframe: Baseline to week 24

Population: FACIT-fatigue analysis set

The FACIT-Fatigue scale was a 13-item self-administered questionnaire that assesses both the physical and functional consequences of fatigue. Each question is answered on a 5-point scale, where 0 means "not at all," and 4 means "very much." The FACIT-Fatigue scale score ranges from 0 to 52, with higher scores denoting lower levels of fatigue. Clinically meaningful improvement in fatigue is defined as an increase of ≥ 3 points in the FACIT-Fatigue subscale score, from baseline to EOTP.

Outcome measures

Outcome measures
Measure	Placebo n=42 Participants Participants received placebo subcutaneous injection every 3 weeks (Q3W) for 24 weeks.	Darbepoetin Alfa n=90 Participants Participants received darbepoetin alfa 500 µg Q3W for 24 weeks.
Percentage of Participants With a Clinically Meaningful Improvement in Fatigue	31.0 percentage of participants Interval 17.62 to 47.09	35.6 percentage of participants Interval 25.74 to 46.35

Adverse Events

Placebo

Serious events: 8 serious events

Other events: 25 other events

Deaths: 0 deaths

Darbepoetin Alfa

Serious events: 11 serious events

Other events: 56 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Placebo n=48 participants at risk Participants received placebo subcutaneous injection every 3 weeks (Q3W) for 24 weeks.	Darbepoetin Alfa n=98 participants at risk Participants received darbepoetin alfa 500 µg Q3W for 24 weeks.
General disorders Asthenia	10.4% 5/48 • From first dose of study drug to 24 weeks for participants who continued into the active treatment period or until 30 days after last dose (maximum of 28 weeks) for participants who did not continue. One participant randomized to the Placebo arm inadvertently received one 200 µg dose of darbepoetin alfa and is reported in the Darbepoetin alfa group for adverse events. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	12.2% 12/98 • From first dose of study drug to 24 weeks for participants who continued into the active treatment period or until 30 days after last dose (maximum of 28 weeks) for participants who did not continue. One participant randomized to the Placebo arm inadvertently received one 200 µg dose of darbepoetin alfa and is reported in the Darbepoetin alfa group for adverse events. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
General disorders Fatigue	8.3% 4/48 • From first dose of study drug to 24 weeks for participants who continued into the active treatment period or until 30 days after last dose (maximum of 28 weeks) for participants who did not continue. One participant randomized to the Placebo arm inadvertently received one 200 µg dose of darbepoetin alfa and is reported in the Darbepoetin alfa group for adverse events. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	17.3% 17/98 • From first dose of study drug to 24 weeks for participants who continued into the active treatment period or until 30 days after last dose (maximum of 28 weeks) for participants who did not continue. One participant randomized to the Placebo arm inadvertently received one 200 µg dose of darbepoetin alfa and is reported in the Darbepoetin alfa group for adverse events. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
General disorders Oedema peripheral	8.3% 4/48 • From first dose of study drug to 24 weeks for participants who continued into the active treatment period or until 30 days after last dose (maximum of 28 weeks) for participants who did not continue. One participant randomized to the Placebo arm inadvertently received one 200 µg dose of darbepoetin alfa and is reported in the Darbepoetin alfa group for adverse events. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	3.1% 3/98 • From first dose of study drug to 24 weeks for participants who continued into the active treatment period or until 30 days after last dose (maximum of 28 weeks) for participants who did not continue. One participant randomized to the Placebo arm inadvertently received one 200 µg dose of darbepoetin alfa and is reported in the Darbepoetin alfa group for adverse events. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
General disorders Pyrexia	2.1% 1/48 • From first dose of study drug to 24 weeks for participants who continued into the active treatment period or until 30 days after last dose (maximum of 28 weeks) for participants who did not continue. One participant randomized to the Placebo arm inadvertently received one 200 µg dose of darbepoetin alfa and is reported in the Darbepoetin alfa group for adverse events. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	9.2% 9/98 • From first dose of study drug to 24 weeks for participants who continued into the active treatment period or until 30 days after last dose (maximum of 28 weeks) for participants who did not continue. One participant randomized to the Placebo arm inadvertently received one 200 µg dose of darbepoetin alfa and is reported in the Darbepoetin alfa group for adverse events. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Nasopharyngitis	6.2% 3/48 • From first dose of study drug to 24 weeks for participants who continued into the active treatment period or until 30 days after last dose (maximum of 28 weeks) for participants who did not continue. One participant randomized to the Placebo arm inadvertently received one 200 µg dose of darbepoetin alfa and is reported in the Darbepoetin alfa group for adverse events. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	8.2% 8/98 • From first dose of study drug to 24 weeks for participants who continued into the active treatment period or until 30 days after last dose (maximum of 28 weeks) for participants who did not continue. One participant randomized to the Placebo arm inadvertently received one 200 µg dose of darbepoetin alfa and is reported in the Darbepoetin alfa group for adverse events. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Musculoskeletal and connective tissue disorders Arthralgia	6.2% 3/48 • From first dose of study drug to 24 weeks for participants who continued into the active treatment period or until 30 days after last dose (maximum of 28 weeks) for participants who did not continue. One participant randomized to the Placebo arm inadvertently received one 200 µg dose of darbepoetin alfa and is reported in the Darbepoetin alfa group for adverse events. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	6.1% 6/98 • From first dose of study drug to 24 weeks for participants who continued into the active treatment period or until 30 days after last dose (maximum of 28 weeks) for participants who did not continue. One participant randomized to the Placebo arm inadvertently received one 200 µg dose of darbepoetin alfa and is reported in the Darbepoetin alfa group for adverse events. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Musculoskeletal and connective tissue disorders Back pain	4.2% 2/48 • From first dose of study drug to 24 weeks for participants who continued into the active treatment period or until 30 days after last dose (maximum of 28 weeks) for participants who did not continue. One participant randomized to the Placebo arm inadvertently received one 200 µg dose of darbepoetin alfa and is reported in the Darbepoetin alfa group for adverse events. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	8.2% 8/98 • From first dose of study drug to 24 weeks for participants who continued into the active treatment period or until 30 days after last dose (maximum of 28 weeks) for participants who did not continue. One participant randomized to the Placebo arm inadvertently received one 200 µg dose of darbepoetin alfa and is reported in the Darbepoetin alfa group for adverse events. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	6.2% 3/48 • From first dose of study drug to 24 weeks for participants who continued into the active treatment period or until 30 days after last dose (maximum of 28 weeks) for participants who did not continue. One participant randomized to the Placebo arm inadvertently received one 200 µg dose of darbepoetin alfa and is reported in the Darbepoetin alfa group for adverse events. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/98 • From first dose of study drug to 24 weeks for participants who continued into the active treatment period or until 30 days after last dose (maximum of 28 weeks) for participants who did not continue. One participant randomized to the Placebo arm inadvertently received one 200 µg dose of darbepoetin alfa and is reported in the Darbepoetin alfa group for adverse events. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/48 • From first dose of study drug to 24 weeks for participants who continued into the active treatment period or until 30 days after last dose (maximum of 28 weeks) for participants who did not continue. One participant randomized to the Placebo arm inadvertently received one 200 µg dose of darbepoetin alfa and is reported in the Darbepoetin alfa group for adverse events. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	5.1% 5/98 • From first dose of study drug to 24 weeks for participants who continued into the active treatment period or until 30 days after last dose (maximum of 28 weeks) for participants who did not continue. One participant randomized to the Placebo arm inadvertently received one 200 µg dose of darbepoetin alfa and is reported in the Darbepoetin alfa group for adverse events. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Nervous system disorders Dizziness	6.2% 3/48 • From first dose of study drug to 24 weeks for participants who continued into the active treatment period or until 30 days after last dose (maximum of 28 weeks) for participants who did not continue. One participant randomized to the Placebo arm inadvertently received one 200 µg dose of darbepoetin alfa and is reported in the Darbepoetin alfa group for adverse events. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	5.1% 5/98 • From first dose of study drug to 24 weeks for participants who continued into the active treatment period or until 30 days after last dose (maximum of 28 weeks) for participants who did not continue. One participant randomized to the Placebo arm inadvertently received one 200 µg dose of darbepoetin alfa and is reported in the Darbepoetin alfa group for adverse events. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Nervous system disorders Headache	2.1% 1/48 • From first dose of study drug to 24 weeks for participants who continued into the active treatment period or until 30 days after last dose (maximum of 28 weeks) for participants who did not continue. One participant randomized to the Placebo arm inadvertently received one 200 µg dose of darbepoetin alfa and is reported in the Darbepoetin alfa group for adverse events. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	7.1% 7/98 • From first dose of study drug to 24 weeks for participants who continued into the active treatment period or until 30 days after last dose (maximum of 28 weeks) for participants who did not continue. One participant randomized to the Placebo arm inadvertently received one 200 µg dose of darbepoetin alfa and is reported in the Darbepoetin alfa group for adverse events. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Psychiatric disorders Insomnia	6.2% 3/48 • From first dose of study drug to 24 weeks for participants who continued into the active treatment period or until 30 days after last dose (maximum of 28 weeks) for participants who did not continue. One participant randomized to the Placebo arm inadvertently received one 200 µg dose of darbepoetin alfa and is reported in the Darbepoetin alfa group for adverse events. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/98 • From first dose of study drug to 24 weeks for participants who continued into the active treatment period or until 30 days after last dose (maximum of 28 weeks) for participants who did not continue. One participant randomized to the Placebo arm inadvertently received one 200 µg dose of darbepoetin alfa and is reported in the Darbepoetin alfa group for adverse events. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Respiratory, thoracic and mediastinal disorders Dyspnoea	4.2% 2/48 • From first dose of study drug to 24 weeks for participants who continued into the active treatment period or until 30 days after last dose (maximum of 28 weeks) for participants who did not continue. One participant randomized to the Placebo arm inadvertently received one 200 µg dose of darbepoetin alfa and is reported in the Darbepoetin alfa group for adverse events. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	5.1% 5/98 • From first dose of study drug to 24 weeks for participants who continued into the active treatment period or until 30 days after last dose (maximum of 28 weeks) for participants who did not continue. One participant randomized to the Placebo arm inadvertently received one 200 µg dose of darbepoetin alfa and is reported in the Darbepoetin alfa group for adverse events. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	10.4% 5/48 • From first dose of study drug to 24 weeks for participants who continued into the active treatment period or until 30 days after last dose (maximum of 28 weeks) for participants who did not continue. One participant randomized to the Placebo arm inadvertently received one 200 µg dose of darbepoetin alfa and is reported in the Darbepoetin alfa group for adverse events. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	6.1% 6/98 • From first dose of study drug to 24 weeks for participants who continued into the active treatment period or until 30 days after last dose (maximum of 28 weeks) for participants who did not continue. One participant randomized to the Placebo arm inadvertently received one 200 µg dose of darbepoetin alfa and is reported in the Darbepoetin alfa group for adverse events. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.

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