Safety and Efficacy of Peginesatide Injection for the Maintenance of Anemia in Chronic Renal Failure Participants Who Are on Hemodialysis or Do Not Require Dialysis and Previously Treated With Darbepoetin Alfa.

• Sponsor: Takeda (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00752609
• Collaborator: Affymax (Industry)
• Enrollment: 102
• Locations: 10
• Arm: 1
• Duration (Months): 15
• Patients Per Site: 10.2
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

The purpose of this study is to determine the efficacy and safety of Peginesatide Injection for the maintenance of anemia in patients with chronic renal failure who are on hemodialysis or do not require dialysis and who were previously treated with Darbepoetin Alfa.

Condition or Disease	Intervention/Treatment	Phase
Anemia	Drug: Peginesatide	Phase 2

Detailed Description

Anemia, resulting primarily from insufficient production of erythropoietin to support erythropoiesis, is a common consequence of chronic renal failure. Both North America and Europe have established clinical practice guidelines for the treatment and hemoglobin targets in chronic renal failure/chronic kidney disease patients. These guidelines recommend the use of erythropoiesis-stimulating agents (ESAs). The benefits of ESA therapy include reduced fatigue, improved quality of life, decreased cardiovascular mortality risk and improved cardiovascular function. An increased risk of death and serious cardiovascular and thromboembolic events, including myocardial infarction, stroke, congestive heart failure, and hemodialysis graft occlusion have been observed in controlled clinical trials of ESAs when administered to target hemoglobin levels of ≥13.5 g/dL. The vast majority of patients receiving hemodialysis receive ESA therapy to treat their anemia and most patients begin ESA therapy prior to any requirement for dialysis.

Anemia of chronic renal failure is due to several factors, primarily the inability of the diseased kidneys to produce adequate amounts of endogenous erythropoietin. Ancillary factors also include the shortened lifespan of red blood cells, iron and other nutritional deficiencies, infection, and inflammation. The prevalence of anemia increases with progressive deterioration of renal function, and affects more than 90% of patients with chronic renal failure Stage 5 (End Stage Renal Disease). Anemia is associated with increased mortality, increased likelihood of hospitalization, reduced cognitive function and exercise capacity, increased left ventricular hypertrophy and heart failure. Treatment of anemia reduces morbidity and mortality risks and may improve quality of life.

Erythropoiesis stimulating agents have been established as a treatment for anemia in chronic renal failure participants, and have improved the management of anemia over alternatives such as transfusion. Peginesatide (hematide) is a parenteral formulation being developed for the correction of anemia in patients with chronic renal failure, and binds to and activates the human erythropoietin receptor and stimulates erythropoiesis in human red cell precursors in a manner similar to other known erythropoiesis-stimulating agents.

Participants in this study received variable doses of peginesatide injection once every four weeks. Total commitment time for this study was about 30 weeks.

Study Design

• Study Type: Interventional
• Actual Enrollment: 102 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2 Study of the Safety and Efficacy of Hematide Injection for the Maintenance Treatment of Anemia in Subjects With Chronic Renal Failure Who Are on Hemodialysis or Do Not Require Dialysis and Previously Treated With Darbepoetin Alfa
• Study Start Date: Sep 1, 2008
• Actual Primary Completion Date: Dec 1, 2009
• Actual Study Completion Date: Dec 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Peginesatide	Drug: Peginesatide; Peginesatide 0.04 to 0.16 mg/kg, subcutaneous or intravenous injection, once every 4 weeks for up to 24 weeks. Initial dose based on patient's previous total weekly darbepoetin alfa dose, and thereafter could be adjusted to maintain hemoglobin values in the target range of 10 to 12 g/dL and ±1.5 g/dL from Baseline.; Other Names: Hematide AF37702 Omontys

Outcome Measures

Primary Outcome Measures

1. Mean Change in Hemoglobin Between Baseline and the Evaluation Period [Baseline and Week 19 to Week 24.]

   Mean change in Hemoglobin between Baseline (the mean of the 4 most recent hemoglobin values prior to enrollment and the hemoglobin on the day of enrollment) and the Evaluation Period (mean hemoglobin from Weeks 19 to 24).

Secondary Outcome Measures

1. Percentage of Participants With Hemoglobin Within the Target Range of 10.0 to 12.0 g/dL During the Evaluation Period [Week 19 to Week 24]

   Mean hemoglobin was calculated from measurements taken during the Evaluation Period from Week 19 to Week 24. The target hemoglobin range was between 10.0 to 12.0 g/dL. The 95% confidence interval was calculated from the normal approximation with continuity correction.

2. Percentage of Participants With a Change in Hemoglobin From Baseline to the Evaluation Period Within 1 g/dL [Baseline and Week 19 to Week 24.]

   Percentage of participants with a mean change in hemoglobin between Baseline (the mean of the 4 most recent hemoglobin values prior to enrollment and the hemoglobin on the day of enrollment) and the Evaluation Period (mean hemoglobin measured at Weeks 19 to 24) of less than or equal ± 1 g/dL. The 95% confidence interval was calculated from the normal approximation with continuity correction.

3. Percentage of Participants With Red Blood Cell Transfusions [Up to 24 weeks.]

   The percentage of participants who received one or more red blood cell transfusions, including packed red blood cells and whole blood transfusions, during the Titration Period (Weeks 0 - 18) and Evaluation Period (Weeks 19 -24). 95% Confidence Intervals were calculated from the normal approximation with continuity correction.

4. Mean Hemoglobin During 4-week Intervals [Up to 24 weeks.]

   Hemoglobin was measured every 2 weeks during the Titration Period (Weeks 0-18) and weekly during the Evaluation Period (Weeks 19-24).

5. Percentage of Participants With Target Hemoglobin of 10.0 to 12.0 g/dL by 4-week Intervals. [Up to 24 weeks.]

   Percentage of participants with mean hemoglobin levels falling between the target level of 10.0 to 12.0 g/dL during 4-week study intervals. Hemoglobin was measured every 2 weeks during the Titration Period (Weeks 0-18) and weekly during the Evaluation Period (Weeks 19-24). 95% Confidence Intervals were calculated from the normal approximation with continuity correction.

6. Percentage of Participants With Dose Adjustments During the Study [From Week 4 to Week 20]

   The peginesatide dose was adjusted to maintain Hemoglobin values in the target range of 10 to 12 g/dL and ±1.5 g/dL from Baseline during the Titration Period (Weeks 0-18) and Evaluation Period (Weeks 19-24). A dose was classified as adjusted if it was not within 20% of the previous dose. A dose was classified as increased or decreased if it was >20% higher or >20% lower respectively, than the previous dose.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 90 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. The patient was a man or woman 18 to 90 years of age, inclusive.

2. The patient had CKD and met 1 of the following criteria:

3. Had been on dialysis for ≥6 months prior to enrollment, or

4. Had not yet begun dialysis (hemodialysis or peritoneal dialysis) and was not anticipated to require initiation of dialysis during participation in the study.

5. The patient was on stable darbepoetin alfa maintenance therapy (either SC or IV) continuously for a minimum of 8 weeks prior to enrollment.

6. The patient had 4 consecutive Hb values with a mean ≥10.0 and ≤12.0 g/dL during screening period, with the difference between the mean of the first 2 consecutive Hb values and the mean of the last 2 consecutive values being ≤1.0 g/dL.

Exclusion Criteria:

1. The patient had known bleeding or coagulation disorder.

2. The patient had known hematologic disease or cause of anemia other than renal disease (i.e., pure red cell aplasia, homozygous sickle-cell disease, thalassemia, multiplemyeloma, hemolytic anemia, and myelodysplastic syndrome).

3. The patient had received a recent course of intensive iron replacement (i.e., more than 500 mg IV in the 28 days prior to enrollment).

4. The patient had advanced chronic CKD defined by New York Heart Association Class III or IV.

5. The patient had a known history of seizure disorder or received antiepileptic medication for a seizure disorder within 6 months prior to enrollment.

6. The patient had a scheduled kidney transplant. Patients currently on a transplant waiting list were not excluded, unless there was an identified donor.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Los Angeles	California	United States
2		Sacramento	California	United States
3		San Diego	California	United States
4		Middlebury	Connecticut	United States
5		Lauderdale Lakes	Florida	United States
6		Shreveport	Louisiana	United States
7		Dearborn	Michigan	United States
8		Columbus	Mississippi	United States
9		Mineola	New York	United States
10		Arlington	Texas	United States

Sponsors and Collaborators

• Takeda
• Affymax

Investigators

• Study Director: Medical Director, Takeda

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Takeda
• ClinicalTrials.gov Identifier: NCT00752609
• Other Study ID Numbers: AFX01_202; 2008-003459-64; U1111-1114-1500
• First Posted: Sep 15, 2008
• Last Update Posted: Jul 27, 2012
• Last Verified: Jun 1, 2012

• Keywords provided by Takeda: Anemia; Drug Therapy; Hemodialysis; Kidney Failure
• Additional relevant MeSH terms: Renal Insufficiency; Kidney Failure, Chronic; Anemia

Study Results

Participant Flow

Recruitment Details	Participants enrolled at 18 investigative sites in the United Kingdom, Italy, Australia, and the United States from 22 September 2008 to 24 December 2009.
Pre-assignment Detail	Participants with a diagnosis of chronic renal failure (on hemodialysis or not on dialysis) and receiving stable Darbepoetin alfa maintenance therapy were enrolled into one treatment group (peginesatide injection).

Arm/Group Title	Peginesatide - On Dialysis	Peginesatide - Not on Dialysis
Arm/Group Description	Participants on dialysis received peginesatide 0.04 to 0.16 mg/kg, subcutaneous or intravenous injection, once every 4 weeks for up to 24 weeks. Initial dose based on patient's previous total weekly darbepoetin alfa dose, and thereafter could be adjusted to maintain hemoglobin values in the target range of 10 to 12 g/dL and ±1.5 g/dL from Baseline.	Participants not on dialysis received peginesatide 0.04 to 0.16 mg/kg, subcutaneous or intravenous injection, once every 4 weeks for up to 24 weeks. Initial dose based on patient's previous total weekly darbepoetin alfa dose, and thereafter could be adjusted to maintain hemoglobin values in the target range of 10 to 12 g/dL and ±1.5 g/dL from Baseline.
Period Title: Overall Study
STARTED	53	49
Full Analysis Set	52	49
COMPLETED	44	47
NOT COMPLETED	9	2

Baseline Characteristics

Arm/Group Title	Peginesatide - On Dialysis	Peginesatide - Not on Dialysis	Total
Arm/Group Description	Participants on dialysis received peginesatide 0.04 to 0.16 mg/kg, subcutaneous or intravenous injection, once every 4 weeks for up to 24 weeks. Initial dose based on patient's previous total weekly darbepoetin alfa dose, and thereafter could be adjusted to maintain hemoglobin values in the target range of 10 to 12 g/dL and ±1.5 g/dL from Baseline.	Participants not on dialysis received peginesatide 0.04 to 0.16 mg/kg, subcutaneous or intravenous injection, once every 4 weeks for up to 24 weeks. Initial dose based on patient's previous total weekly darbepoetin alfa dose, and thereafter could be adjusted to maintain hemoglobin values in the target range of 10 to 12 g/dL and ±1.5 g/dL from Baseline.	Total of all reporting groups
Overall Participants	52	49	101
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	66.4 (12.60)	68.6 (12.07)	67.5 (12.33)
Age, Customized (participants) [Number]
< 65 years	22 42.3%	18 36.7%	40 39.6%
≥65 - <75 years	13 25%	13 26.5%	26 25.7%
≥ 75	17 32.7%	18 36.7%	35 34.7%
Sex: Female, Male (Count of Participants)
Female	17 32.7%	33 67.3%	50 49.5%
Male	35 67.3%	16 32.7%	51 50.5%

Outcome Measures

1. Primary Outcome

Title	Mean Change in Hemoglobin Between Baseline and the Evaluation Period
Description	Mean change in Hemoglobin between Baseline (the mean of the 4 most recent hemoglobin values prior to enrollment and the hemoglobin on the day of enrollment) and the Evaluation Period (mean hemoglobin from Weeks 19 to 24).
Time Frame	Baseline and Week 19 to Week 24.

Outcome Measure Data

Analysis Population Description

The Full Analysis Set including all patients who received at least 1 dose of study drug where data was available (indicated by N).

Arm/Group Title	Peginesatide - On Dialysis	Peginesatide - Not on Dialysis
Arm/Group Description	Participants on dialysis received peginesatide 0.04 to 0.16 mg/kg, subcutaneous or intravenous injection, once every 4 weeks for up to 24 weeks. Initial dose based on patient's previous total weekly darbepoetin alfa dose, and thereafter could be adjusted to maintain hemoglobin values in the target range of 10 to 12 g/dL and ±1.5 g/dL from Baseline.	Participants not on dialysis received peginesatide 0.04 to 0.16 mg/kg, subcutaneous or intravenous injection, once every 4 weeks for up to 24 weeks. Initial dose based on patient's previous total weekly darbepoetin alfa dose, and thereafter could be adjusted to maintain hemoglobin values in the target range of 10 to 12 g/dL and ±1.5 g/dL from Baseline.
Measure Participants	52	49
Baseline [N=52, 49]	11.22 (0.514)	11.11 (0.447)
Evaluation Period [N=45, 47]	10.78 (0.845)	11.64 (0.673)
Change from Baseline [N=45, 47]	-0.42 (0.761)	0.49 (0.769)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Peginesatide - On Dialysis
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean change from baseline
	Estimated Value	-0.42
	Confidence Interval	(2-Sided) 95%; -0.65 to -0.19
	Parameter Dispersion	Type: Value:
	Estimation Comments	A two-sided 95% CI of the estimated mean change from Baseline in hemoglobin was derived from the t-distribution.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Peginesatide - Not on Dialysis
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean change from baseline
	Estimated Value	0.49
	Confidence Interval	(2-Sided) 95%; 0.26 to 0.71
	Parameter Dispersion	Type: Value:
	Estimation Comments	A two-sided 95% CI of the estimated mean change from Baseline in hemoglobin was derived from the t-distribution.

2. Secondary Outcome

Title	Percentage of Participants With Hemoglobin Within the Target Range of 10.0 to 12.0 g/dL During the Evaluation Period
Description	Mean hemoglobin was calculated from measurements taken during the Evaluation Period from Week 19 to Week 24. The target hemoglobin range was between 10.0 to 12.0 g/dL. The 95% confidence interval was calculated from the normal approximation with continuity correction.
Time Frame	Week 19 to Week 24

Outcome Measure Data

Analysis Population Description

Full Analysis Set where data was available.

Arm/Group Title	Peginesatide - On Dialysis	Peginesatide - Not on Dialysis
Arm/Group Description	Participants on dialysis received peginesatide 0.04 to 0.16 mg/kg, subcutaneous or intravenous injection, once every 4 weeks for up to 24 weeks. Initial dose based on patient's previous total weekly darbepoetin alfa dose, and thereafter could be adjusted to maintain hemoglobin values in the target range of 10 to 12 g/dL and ±1.5 g/dL from Baseline.	Participants not on dialysis received peginesatide 0.04 to 0.16 mg/kg, subcutaneous or intravenous injection, once every 4 weeks for up to 24 weeks. Initial dose based on patient's previous total weekly darbepoetin alfa dose, and thereafter could be adjusted to maintain hemoglobin values in the target range of 10 to 12 g/dL and ±1.5 g/dL from Baseline.
Measure Participants	45	47
Number (95% Confidence Interval) [percentage of participants]	73.3 141%	68.1 139%

3. Secondary Outcome

Title	Percentage of Participants With a Change in Hemoglobin From Baseline to the Evaluation Period Within 1 g/dL
Description	Percentage of participants with a mean change in hemoglobin between Baseline (the mean of the 4 most recent hemoglobin values prior to enrollment and the hemoglobin on the day of enrollment) and the Evaluation Period (mean hemoglobin measured at Weeks 19 to 24) of less than or equal ± 1 g/dL. The 95% confidence interval was calculated from the normal approximation with continuity correction.
Time Frame	Baseline and Week 19 to Week 24.

Outcome Measure Data

Analysis Population Description

Full analysis set where data was available.

Arm/Group Title	Peginesatide - On Dialysis	Peginesatide - Not on Dialysis
Arm/Group Description	Participants on dialysis received peginesatide 0.04 to 0.16 mg/kg, subcutaneous or intravenous injection, once every 4 weeks for up to 24 weeks. Initial dose based on patient's previous total weekly darbepoetin alfa dose, and thereafter could be adjusted to maintain hemoglobin values in the target range of 10 to 12 g/dL and ±1.5 g/dL from Baseline.	Participants not on dialysis received peginesatide 0.04 to 0.16 mg/kg, subcutaneous or intravenous injection, once every 4 weeks for up to 24 weeks. Initial dose based on patient's previous total weekly darbepoetin alfa dose, and thereafter could be adjusted to maintain hemoglobin values in the target range of 10 to 12 g/dL and ±1.5 g/dL from Baseline.
Measure Participants	45	47
Number (95% Confidence Interval) [percentage of participants]	80.0 153.8%	68.1 139%

4. Secondary Outcome

Title	Percentage of Participants With Red Blood Cell Transfusions
Description	The percentage of participants who received one or more red blood cell transfusions, including packed red blood cells and whole blood transfusions, during the Titration Period (Weeks 0 - 18) and Evaluation Period (Weeks 19 -24). 95% Confidence Intervals were calculated from the normal approximation with continuity correction.
Time Frame	Up to 24 weeks.

Outcome Measure Data

Analysis Population Description

Full Analysis Set.

Arm/Group Title	Peginesatide - On Dialysis	Peginesatide - Not on Dialysis
Arm/Group Description	Participants on dialysis received peginesatide 0.04 to 0.16 mg/kg, subcutaneous or intravenous injection, once every 4 weeks for up to 24 weeks. Initial dose based on patient's previous total weekly darbepoetin alfa dose, and thereafter could be adjusted to maintain hemoglobin values in the target range of 10 to 12 g/dL and ±1.5 g/dL from Baseline.	Participants not on dialysis received peginesatide 0.04 to 0.16 mg/kg, subcutaneous or intravenous injection, once every 4 weeks for up to 24 weeks. Initial dose based on patient's previous total weekly darbepoetin alfa dose, and thereafter could be adjusted to maintain hemoglobin values in the target range of 10 to 12 g/dL and ±1.5 g/dL from Baseline.
Measure Participants	52	49
Entire study	5.8 11.2%	2.0 4.1%
Titration Period	5.8 11.2%	2.0 4.1%
Evaluation Period	0 0%	0 0%

5. Secondary Outcome

Title	Mean Hemoglobin During 4-week Intervals
Description	Hemoglobin was measured every 2 weeks during the Titration Period (Weeks 0-18) and weekly during the Evaluation Period (Weeks 19-24).
Time Frame	Up to 24 weeks.

Outcome Measure Data

Analysis Population Description

Full Analysis Set where data was available for each time interval (indicated by N).

Arm/Group Title	Peginesatide - On Dialysis	Peginesatide - Not on Dialysis
Arm/Group Description	Participants on dialysis received peginesatide 0.04 to 0.16 mg/kg, subcutaneous or intravenous injection, once every 4 weeks for up to 24 weeks. Initial dose based on patient's previous total weekly darbepoetin alfa dose, and thereafter could be adjusted to maintain hemoglobin values in the target range of 10 to 12 g/dL and ±1.5 g/dL from Baseline.	Participants not on dialysis received peginesatide 0.04 to 0.16 mg/kg, subcutaneous or intravenous injection, once every 4 weeks for up to 24 weeks. Initial dose based on patient's previous total weekly darbepoetin alfa dose, and thereafter could be adjusted to maintain hemoglobin values in the target range of 10 to 12 g/dL and ±1.5 g/dL from Baseline.
Measure Participants	52	49
Week 1-4 [N=52, 49]	11.54 (0.728)	11.74 (0.863)
Week 5-8 [N=49, 49]	11.16 (0.876)	11.94 (0.917)
Week 9-12 [N=49, 47]	10.99 (0.919)	11.95 (0.837)
Week 13-16 [N=47, 46]	10.64 (0.975)	11.95 (0.815)
Week 17-20 [N=46, 47]	10.78 (0.989)	11.84 (0.747)
Week 21-24 [N=44, 47]	10.81 (0.827)	11.58 (0.687)

6. Secondary Outcome

Title	Percentage of Participants With Target Hemoglobin of 10.0 to 12.0 g/dL by 4-week Intervals.
Description	Percentage of participants with mean hemoglobin levels falling between the target level of 10.0 to 12.0 g/dL during 4-week study intervals. Hemoglobin was measured every 2 weeks during the Titration Period (Weeks 0-18) and weekly during the Evaluation Period (Weeks 19-24). 95% Confidence Intervals were calculated from the normal approximation with continuity correction.
Time Frame	Up to 24 weeks.

Outcome Measure Data

Analysis Population Description

Full analysis set where data was available for each time interval (indicated by N).

Arm/Group Title	Peginesatide - On Dialysis	Peginesatide - Not on Dialysis
Arm/Group Description	Participants on dialysis received peginesatide 0.04 to 0.16 mg/kg, subcutaneous or intravenous injection, once every 4 weeks for up to 24 weeks. Initial dose based on patient's previous total weekly darbepoetin alfa dose, and thereafter could be adjusted to maintain hemoglobin values in the target range of 10 to 12 g/dL and ±1.5 g/dL from Baseline.	Participants not on dialysis received peginesatide 0.04 to 0.16 mg/kg, subcutaneous or intravenous injection, once every 4 weeks for up to 24 weeks. Initial dose based on patient's previous total weekly darbepoetin alfa dose, and thereafter could be adjusted to maintain hemoglobin values in the target range of 10 to 12 g/dL and ±1.5 g/dL from Baseline.
Measure Participants	52	49
Week 1-4 [N=52, 49]	71.2 136.9%	69.4 141.6%
Week 5-8 [N= 49, 49]	81.6 156.9%	51.0 104.1%
Week 9-12 [N= 49, 47]	77.6 149.2%	44.7 91.2%
Week 13-16 [N= 47, 46]	74.5 143.3%	52.2 106.5%
Week 17-20 [N=46, 47]	69.6 133.8%	59.6 121.6%
Week 21-24 [N=44, 47]	79.5 152.9%	63.8 130.2%

7. Secondary Outcome

Title	Percentage of Participants With Dose Adjustments During the Study
Description	The peginesatide dose was adjusted to maintain Hemoglobin values in the target range of 10 to 12 g/dL and ±1.5 g/dL from Baseline during the Titration Period (Weeks 0-18) and Evaluation Period (Weeks 19-24). A dose was classified as adjusted if it was not within 20% of the previous dose. A dose was classified as increased or decreased if it was >20% higher or >20% lower respectively, than the previous dose.
Time Frame	From Week 4 to Week 20

Outcome Measure Data

Analysis Population Description

Safety Analysis set, which included all patients who received at least 1 dose of study drug. N indicates the number of patients with study drug administered during the period after excluding the initial dose of study drug and excluding the first dose after a restart of study drug and is the denominator for percentage calculations.

Arm/Group Title	IV Peginesatide - On Dialysis	SC Peginesatide - On Dialysis	Peginesatide - Not on Dialysis
Arm/Group Description	Participants on dialysis received 0.04 to 0.16 mg/kg Peginesatide intravenous (IV) injection once every 4 weeks for 24 weeks. Initial dose based on patient's previous total weekly darbepoetin alfa dose, and thereafter could be adjusted to maintain hemoglobin values in the target range of 10 to 12 g/dL and ±1.5 g/dL from Baseline.	Participants on dialysis received 0.04 to 0.16 mg/kg Peginesatide subcutaneous (SC) injection, once every 4 weeks for 24 weeks. Initial dose based on patient's previous total weekly darbepoetin alfa dose, and thereafter could be adjusted to maintain hemoglobin values in the target range of 10 to 12 g/dL and ±1.5 g/dL from Baseline.	Participants not on dialysis received 0.04 to 0.16 mg/kg Peginesatide subcutaneous injection, once every 4 weeks for 24 weeks. Initial dose based on patient's previous total weekly darbepoetin alfa dose, and thereafter could be adjusted to maintain hemoglobin values in the target range of 10 to 12 g/dL and ±1.5 g/dL from Baseline.
Measure Participants	47	5	49
Any adjustment in Titration Period [N=44, 5, 49]	81.8 157.3%	80.0 163.3%	81.6 80.8%
Any adjustment in Evaluation Period [N=38, 5, 44]	31.6 60.8%	60.0 122.4%	43.2 42.8%
Any adjustment during entire study [N=44, 5, 49]	90.9 174.8%	80.0 163.3%	87.8 86.9%
Dose increased in Titration Period [N=44, 5, 49]	56.8 109.2%	40.0 81.6%	10.2 10.1%
Dose increased in Evaluation Period [N=38, 5, 44]	21.1 40.6%	40.0 81.6%	2.3 2.3%
Dose increased during entire study [N=44, 5, 49]	65.9 126.7%	60.0 122.4%	12.2 12.1%
Dose decreased in Titration Period [N=44, 5, 49]	50.0 96.2%	60.0 122.4%	73.5 72.8%
Dose decreased in Evaluation Period [N=38, 5, 44]	13.2 25.4%	20.0 40.8%	40.9 40.5%
Dose decreased during entire study [N=44, 5, 49]	59.1 113.7%	60.0 122.4%	79.6 78.8%

Adverse Events

Time Frame	Treatment-emergent adverse events are adverse events that occurred on or after the day of the first dose of peginesatide injection through the Follow-up phone call, which occurred within 28 days after the last dose.
Adverse Event Reporting Description	At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Arm/Group Title	Peginesatide - On Dialysis		Peginesatide - Not on Dialysis
Arm/Group Description	Participants on dialysis received peginesatide 0.04 to 0.16 mg/kg, subcutaneous or intravenous injection, once every 4 weeks for up to 24 weeks. Initial dose based on patient's previous total weekly darbepoetin alfa dose, and thereafter could be adjusted to maintain hemoglobin values in the target range of 10 to 12 g/dL and ±1.5 g/dL from Baseline.		Participants not on dialysis received peginesatide 0.04 to 0.16 mg/kg, subcutaneous or intravenous injection, once every 4 weeks for up to 24 weeks. Initial dose based on patient's previous total weekly darbepoetin alfa dose, and thereafter could be adjusted to maintain hemoglobin values in the target range of 10 to 12 g/dL and ±1.5 g/dL from Baseline.
All Cause Mortality
	Peginesatide - On Dialysis		Peginesatide - Not on Dialysis
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Peginesatide - On Dialysis		Peginesatide - Not on Dialysis
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	16/52 (30.8%)		6/49 (12.2%)
Cardiac disorders
Cardiac failure congestive	1/52 (1.9%)		2/49 (4.1%)
Atrial fibrillation	1/52 (1.9%)		0/49 (0%)
Ischaemic cardiomyopathy	1/52 (1.9%)		0/49 (0%)
Mitral valve incompetence	1/52 (1.9%)		0/49 (0%)
Gastrointestinal disorders
Diarrhoea	1/52 (1.9%)		0/49 (0%)
Gastritis	1/52 (1.9%)		0/49 (0%)
General disorders
Chest pain	2/52 (3.8%)		0/49 (0%)
Hepatobiliary disorders
Cholecystitis acute	1/52 (1.9%)		0/49 (0%)
Cholelithiasis	1/52 (1.9%)		0/49 (0%)
Infections and infestations
Dermo-hypodermitis	1/52 (1.9%)		0/49 (0%)
Infective exacerbation of chronic obstructive airways disease	1/52 (1.9%)		0/49 (0%)
Pneumonia	1/52 (1.9%)		0/49 (0%)
Injury, poisoning and procedural complications
Arteriovenous fistula thrombosis	2/52 (3.8%)		0/49 (0%)
Ankle fracture	1/52 (1.9%)		0/49 (0%)
Arteriovenous fistula site complication	1/52 (1.9%)		0/49 (0%)
Arteriovenous graft thrombosis	1/52 (1.9%)		0/49 (0%)
Fall	1/52 (1.9%)		0/49 (0%)
Humerus fracture	1/52 (1.9%)		0/49 (0%)
Joint dislocation	1/52 (1.9%)		0/49 (0%)
Metabolism and nutrition disorders
Hyperkalaemia	2/52 (3.8%)		0/49 (0%)
Fluid overload	1/52 (1.9%)		0/49 (0%)
Metabolic acidosis	1/52 (1.9%)		0/49 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung cancer metastatic	1/52 (1.9%)		0/49 (0%)
Nervous system disorders
Cerebrovascular accident	0/52 (0%)		1/49 (2%)
Convulsion	1/52 (1.9%)		0/49 (0%)
Diabetic neuropathy	0/52 (0%)		1/49 (2%)
Encephalopathy	0/52 (0%)		1/49 (2%)
Ischaemic cerebral infarction	1/52 (1.9%)		0/49 (0%)
Renal and urinary disorders
Renal failure acute	0/52 (0%)		1/49 (2%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	0/52 (0%)		1/49 (2%)
Pleural effusion	1/52 (1.9%)		0/49 (0%)
Surgical and medical procedures
Aortic valve replacement	1/52 (1.9%)		0/49 (0%)
Vascular disorders
Peripheral vascular disorder	1/52 (1.9%)		0/49 (0%)
Other (Not Including Serious) Adverse Events
	Peginesatide - On Dialysis		Peginesatide - Not on Dialysis
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	31/52 (59.6%)		28/49 (57.1%)
Blood and lymphatic system disorders
Anaemia	3/52 (5.8%)		0/49 (0%)
Gastrointestinal disorders
Diarrhoea	8/52 (15.4%)		6/49 (12.2%)
Nausea	6/52 (11.5%)		3/49 (6.1%)
Consitpation	4/52 (7.7%)		2/49 (4.1%)
Vomiting	6/52 (11.5%)		0/49 (0%)
General disorders
Oedema Peripheral	2/52 (3.8%)		6/49 (12.2%)
Astenia	1/52 (1.9%)		3/49 (6.1%)
Chest Discomfort	3/52 (5.8%)		0/49 (0%)
Injection Site Extravasation	3/52 (5.8%)		0/49 (0%)
Infections and infestations
Upper Respiratory Tract Infection	3/52 (5.8%)		6/49 (12.2%)
Sinusitis	0/52 (0%)		3/49 (6.1%)
Injury, poisoning and procedural complications
Thrombosis in Device	4/52 (7.7%)		0/49 (0%)
Vascular Graft Complication	3/52 (5.8%)		0/49 (0%)
Metabolism and nutrition disorders
Decreased Appetite	7/52 (13.5%)		2/49 (4.1%)
Musculoskeletal and connective tissue disorders
Pain in Extremity	1/52 (1.9%)		4/49 (8.2%)
Arthralgia	3/52 (5.8%)		1/49 (2%)
Nervous system disorders
Dizziness	2/52 (3.8%)		5/49 (10.2%)
Headache	4/52 (7.7%)		2/49 (4.1%)
Psychiatric disorders
Insomnia	2/52 (3.8%)		3/49 (6.1%)
Respiratory, thoracic and mediastinal disorders
Cough	4/52 (7.7%)		4/49 (8.2%)
Dyspnoea	3/52 (5.8%)		1/49 (2%)
Vascular disorders
Hypertension	4/52 (7.7%)		3/49 (6.1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.