Darbepoetin Alfa With or Without Iron in Treating Anemia... | NCT00661999

NCT00661999

ID	Type	Description	Link
P30CA015083	U.S. NIH Grant/Contract		View source
MC04CC	Other Identifier	Mayo Clinic Cancer Center
NCI-2009-01226	Registry Identifier	NCI-CTRP
1713-05	Other Identifier	Mayo Clinic IRB

Status Module

Name	Class
National Cancer Institute (NCI)	NIH

Description Module

Detailed Description

OBJECTIVES:

Primary

* To compare the effects of IV iron, oral iron, or placebo in combination with darbepoetin alfa on the hematopoietic response rate, defined as a hemoglobin increment of ≥ 2.0 g/dL from baseline or achievement of hemoglobin of ≥ 11 g/dL in the absence of red blood cell transfusions (RBC) in the preceding 28 days of the treatment period, in cancer patients with chemotherapy-associated anemia.

Secondary

To compare the effects of these regimens on the mean hemoglobin increment from baseline to weeks 7 and 16 in these patients.
To compare the effects of these regimens on the percentage of patients maintaining an average hemoglobin level within the American Society of Hematology/American Society of Clinical Oncology (ASH/ASCO)and National Comprehensive Cancer Network(NCCN) guideline-based target hemoglobin range (11-13 g/dL), once achieving a hemoglobin of ≥ 11 g/dL from week 1 to week 16 in the absence of RBC transfusions in the preceding 28 days of the treatment period.
To compare the effects of intravenously (IV) iron, oral iron, or placebo on the response to darbepoetin alfa, in terms of time to achieving hemoglobin levels of ≥ 11g/dL.
To compare the effects of these regimens on the percentage of patients who require RBC transfusions and the total transfusion needs.
To compare the effects of these regimens on the change in hemoglobin week by week.
To compare the effects of these regimens on quality-of-life changes from baseline to weeks 7 and 16.
To identify if patients with inflammation (as indicated by elevated C-reactive protein (CRP) and serum hepcidin levels or low soluble transferrin receptor (sTfR)/log ferritin ratios) respond differently to darbepoetin alfa and iron therapy than patients without inflammation.

OUTLINE: Patients are stratified according to severity of anemia (mild [hemoglobin ≥ 9.5 g/dL] vs severe [hemoglobin < 9.5 g/dL]), treatment with a platinum-containing regimen (yes vs no), and gender. Patients are randomized to 1 of 3 treatment arms.

Arm I: Patients receive darbepoetin alfa subcutaneously and sodium ferric gluconate complex IV over 90 minutes on day 1.
Arm II: Patients receive darbepoetin alfa as in arm I and oral ferrous sulfate once daily on days 1-21.
Arm III: Patients receive darbepoetin alfa as in arm I and oral placebo once daily on days 1-21.

In all arms, treatment repeats every 21 days for up to 15 weeks in the absence of unacceptable toxicity.

Patients complete quality-of-life (QOL) questionnaires in weeks 1, 7, and 16.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Arm I	Experimental	Patients receive darbepoetin alfa subcutaneously and sodium ferric gluconate complex IV over 90 minutes on day 1. Treatment repeats every 21 days for up to 15 weeks in the absence of unacceptable toxicity.	Biological: darbepoetin alfa Drug: sodium ferric gluconate complex in sucrose
Arm II	Experimental	Patients receive darbepoetin alfa as in arm I and oral ferrous sulfate once daily on days 1-21. Treatment repeats every 21 days for up to 15 weeks in the absence of unacceptable toxicity.	Biological: darbepoetin alfa Dietary Supplement: ferrous sulfate
Arm III	Experimental	Patients receive darbepoetin alfa as in arm I and oral placebo once daily on days 1-21. Treatment repeats every 21 days for up to 15 weeks in the absence of unacceptable toxicity.	Biological: darbepoetin alfa Other: placebo

Name	Type	Description	Arm Group Labels	Other Names
darbepoetin alfa	Biological	Given by injection	Arm I Arm II Arm III

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Hematopoietic Response Rate Defined as the Number of Participants Who Exhibit a Hematopoietic Response	Hematopoietic response was defined as Hemoglobin (Hb) increment of 2.0 g/dL from baseline or achievement of Hb >= 11 g/dL (whichever occurs first) in the absence of red blood cell transfusions during the preceding 28 days during the treatment period.	16 Weeks

Secondary Outcomes

Measure	Description	Time Frame
Percentage of Patients Maintaining an Average Hemoglobin Level Within the National Comprehensive Cancer Network (NCCN) Range (11-13 g/dL) Through Week 16, Once Achieving a Hemoglobin of ≥ 11 g/dL		16 Weeks
Incidence of Patients Receiving at Least One Red Blood Cell (RBC) Transfusions

Eligibility Module

Eligibility Criteria

DISEASE CHARACTERISTICS:

Diagnosis of a non-myeloid cancer (other than non-melanomatous skin cancer)
Receiving or scheduled to receive chemotherapy (biological agents, such as small molecules/tyrosine kinase inhibitors and antibody-based therapies, are allowed)
Has chemotherapy-related anemia (hemoglobin < 11 g/dL)
- No anemia known to be secondary to gastrointestinal bleeding or hemolysis
- No anemia known to be secondary to vitamin B12 or folic acid deficiency
  
  + Vitamin B12 and folic acid deficiency must be ruled out if the mean corpuscular volume (MCV) is > 100 fL
- No anemia secondary to chemotherapy-induced myelodysplastic syndromes
No primary hematologic disorder causing moderate to severe anemia (e.g., congenital dyserythropoietic anemia, homozygous hemoglobin S disease or compound heterozygous sickling states, or thalassemia major)

- Carriers for these disease states are eligible
No first-degree relative with primary hemochromatosis (unless the patient has undergone HFE genotyping and was found to have at least one wild-type allele, while the proband in the family demonstrated to have either the common C282Y or H63D mutation)

PATIENT CHARACTERISTICS:

ECOG performance status 0-2
Ferritin > 20 mcg/L (i.e., not obviously iron deficient)
ALT or AST < 5 times upper limit of normal
Alert, mentally competent, and able to sign informed consent
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception during and for 3 months after completion of study treatment
Willing or able to be randomized and undergo study treatment
Willing or able to fill out quality-of-life forms
No uncontrolled hypertension (i.e., systolic blood pressure [BP] ≥ 180 mm Hg or diastolic BP ≥ 100 mm Hg)
No history of uncontrolled cardiac arrhythmias
No pulmonary embolism or deep venous thrombosis within the past year (unless the patient is on anticoagulation therapy and planning to continue it during study participation)
No known hypersensitivity to darbepoetin alfa, erythropoietin, mammalian cell-derived products, iron, or human albumin
No seizures within the past 3 months
No gastrointestinal conditions expected to cause significant impairment of oral iron, such as untreated celiac disease or amyloidosis involving the gut - Patients with celiac disease who are adhering to a gluten-free diet are eligible

PRIOR CONCURRENT THERAPY:

See Disease Characteristics
More than 3 months since prior darbepoetin alfa, epoetin alfa, or any investigational forms of erythropoietin (e.g., gene-activated erythropoietin or novel erythropoiesis-stimulating protein)
More than 1 year since prior peripheral blood stem cell or bone marrow transplantation
More than 2 weeks since prior red blood cell transfusions
More than 14 days since prior major surgery
No prior gastrectomy or resection of > 100 cm of small intestine
Not planning to undergo stem cell or bone marrow transplantation within the next 6 months

Name	Affiliation	Role
Charles L. Loprinzi, MD	Mayo Clinic	Study Chair
Tom R. Fitch, M.D.	Mayo Clinic	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Mayo Clinic in Arizona		Scottsdale	Arizona		United States
Mayo Clinic

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	DA + IV Iron	Patients receive darbepoetin alfa (DA) subcutaneously and sodium ferric gluconate complex intravenously (IV) over 90 minutes on day 1. Treatment repeats every 21 days for up to 15 weeks in the absence of unacceptable toxicity.
FG001	DA + Oral Iron

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Arm/Group Information

ID	Title	Description
BG000	DA + IV Iron	Patients receive darbepoetin alfa (DA) subcutaneously and sodium ferric gluconate complex intravenously (IV) over 90 minutes on day 1. Treatment repeats every 21 days for up to 15 weeks in the absence of unacceptable toxicity.
BG001	DA + Oral Iron	Patients receive darbepoetin alfa (DA) as in arm I and oral ferrous sulfate once daily on days 1-21. Treatment repeats every 21 days for up to 15 weeks in the absence of unacceptable toxicity.
BG002	DA + Placebo	Patients receive darbepoetin alfa (DA) as in arm I and oral placebo once daily on days 1-21. Treatment repeats every 21 days for up to 15 weeks in the absence of unacceptable toxicity.
BG003	Total	Total of all reporting groups

Units	Counts
Participants	BG000164 BG001163 BG002163 BG003490

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00064± 11 BG00163± 13 BG00263± 11 BG003

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG000109 BG001106 BG002

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0000 BG0013 BG002

Degree of Anemia

Number

Participants

Title

Denominators

Categories

Mild: Hemoglobin>=9.5

Title	Measurements
	BG000123 BG001123 BG002

Platinum-Containing Regimen

Number

Participants

Title

Denominators

Categories

Yes

Title	Measurements
	BG00079 BG00179 BG002

Tumor Type

Number

Participants

Title

Denominators

Categories

Hematologic Neoplasm

Title	Measurements
	BG0006 BG0018 BG002

Weight

Mean

Standard Deviation

Title

Denominators

Categories

Title	Measurements
	BG00077.4± 18.74 BG00179.4± 19.75 BG002

Height

Mean

Standard Deviation

Title

Denominators

Categories

Title	Measurements
	BG000166.9± 9.44 BG001167.7± 8.93 BG002

Baseline Ferritin

Mean

Standard Deviation

µg/L

Title

Denominators

Categories

Title	Measurements
	BG000460.5± 526.99 BG001479.5± 484.15 BG002

Baseline Transferrin Saturation

Mean

Standard Deviation

Percentage Saturation

Title

Denominators

Categories

Title	Measurements
	BG00022.5± 12.81 BG00119.6± 11.7 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Hematopoietic Response Rate Defined as the Number of Participants Who Exhibit a Hematopoietic Response

Hematopoietic response was defined as Hemoglobin (Hb) increment of 2.0 g/dL from baseline or achievement of Hb >= 11 g/dL (whichever occurs first) in the absence of red blood cell transfusions during the preceding 28 days during the treatment period.

Posted

Number

Participants

16 Weeks

ID	Title	Description
OG000	DA + IV Iron	Patients receive darbepoetin alfa (DA) subcutaneously and sodium ferric gluconate complex intravenously (IV) over 90 minutes on day 1. Treatment repeats every 21 days for up to 15 weeks in the absence of unacceptable toxicity.
OG001	DA + Oral Iron	Patients receive darbepoetin alfa (DA) as in arm I and oral ferrous sulfate once daily on days 1-21. Treatment repeats every 21 days for up to 15 weeks in the absence of unacceptable toxicity.
OG002	DA + Placebo	Patients receive darbepoetin alfa (DA) as in arm I and oral placebo once daily on days 1-21. Treatment repeats every 21 days for up to 15 weeks in the absence of unacceptable toxicity.

Units	Counts
Participants	OG000164 OG001163 OG002163

Title

Denominators

Categories

Yes

Title	Measurements
	OG000114 OG001109 OG002106

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG002	With 176 evaluable participants per treatment arm, there would have been >=80% power to detect a difference across two treatment arms of 15% in the primary hematopoietic response endpoint through Fisher's exact test, if the true percentage of patients that experience a hematopoietic response was at least 30% in the superior group, with a 2.5% type I error rate.	Fisher Exact		0.39							95						No	Superiority or Other

Secondary

Percentage of Patients Maintaining an Average Hemoglobin Level Within the National Comprehensive Cancer Network (NCCN) Range (11-13 g/dL) Through Week 16, Once Achieving a Hemoglobin of ≥ 11 g/dL

Posted

Number

Percentage of Participants

16 Weeks

ID	Title	Description
OG000	DA + IV Iron	Patients receive darbepoetin alfa (DA) subcutaneously and sodium ferric gluconate complex intravenously (IV) over 90 minutes on day 1. Treatment repeats every 21 days for up to 15 weeks in the absence of unacceptable toxicity.
OG001	DA + Oral Iron	Patients receive darbepoetin alfa (DA) as in arm I and oral ferrous sulfate once daily on days 1-21. Treatment repeats every 21 days for up to 15 weeks in the absence of unacceptable toxicity.
OG002	DA + Placebo	Patients receive darbepoetin alfa (DA) as in arm I and oral placebo once daily on days 1-21. Treatment repeats every 21 days for up to 15 weeks in the absence of unacceptable toxicity.

Units	Counts
Participants

Secondary

Incidence of Patients Receiving at Least One Red Blood Cell (RBC) Transfusions

Posted

Number

Participants

Week 1 to Week 16

ID	Title	Description
OG000	DA + IV Iron	Patients receive darbepoetin alfa (DA) subcutaneously and sodium ferric gluconate complex intravenously (IV) over 90 minutes on day 1. Treatment repeats every 21 days for up to 15 weeks in the absence of unacceptable toxicity.
OG001	DA + Oral Iron	Patients receive darbepoetin alfa (DA) as in arm I and oral ferrous sulfate once daily on days 1-21. Treatment repeats every 21 days for up to 15 weeks in the absence of unacceptable toxicity.
OG002	DA + Placebo	Patients receive darbepoetin alfa (DA) as in arm I and oral placebo once daily on days 1-21. Treatment repeats every 21 days for up to 15 weeks in the absence of unacceptable toxicity.

Units	Counts
Participants

Secondary

Mean Increment in Hemoglobin Level at Week 7

Value at 7 weeks minus value at baseline.

Posted

Mean

Standard Deviation

g/dL

Baseline and 7 weeks

ID	Title	Description
OG000	DA + IV Iron	Patients receive darbepoetin alfa (DA) subcutaneously and sodium ferric gluconate complex intravenously (IV) over 90 minutes on day 1. Treatment repeats every 21 days for up to 15 weeks in the absence of unacceptable toxicity.
OG001	DA + Oral Iron	Patients receive darbepoetin alfa (DA) as in arm I and oral ferrous sulfate once daily on days 1-21. Treatment repeats every 21 days for up to 15 weeks in the absence of unacceptable toxicity.
OG002	DA + Placebo	Patients receive darbepoetin alfa (DA) as in arm I and oral placebo once daily on days 1-21. Treatment repeats every 21 days for up to 15 weeks in the absence of unacceptable toxicity.

Units	Counts
Participants

Secondary

Mean Increment in Hemoglobin Level at Week 16

Value at 16 weeks minus value at baseline.

Posted

Mean

Standard Deviation

g/dL

Baseline and 16 weeks

ID	Title	Description
OG000	DA + IV Iron	Patients receive darbepoetin alfa (DA) subcutaneously and sodium ferric gluconate complex intravenously (IV) over 90 minutes on day 1. Treatment repeats every 21 days for up to 15 weeks in the absence of unacceptable toxicity.
OG001	DA + Oral Iron	Patients receive darbepoetin alfa (DA) as in arm I and oral ferrous sulfate once daily on days 1-21. Treatment repeats every 21 days for up to 15 weeks in the absence of unacceptable toxicity.
OG002	DA + Placebo	Patients receive darbepoetin alfa (DA) as in arm I and oral placebo once daily on days 1-21. Treatment repeats every 21 days for up to 15 weeks in the absence of unacceptable toxicity.

Units	Counts
Participants

Secondary

Time to Hematopoietic Response

Hematopoietic response was defined as Hb increment of 2.0 g/dL from baseline or achievement of Hb >= 11 g/dL (whichever occurs first) in the absence of red blood cell transfusions during the preceding 28 days during the treatment period.

Posted

Median

95% Confidence Interval

Days

16 weeks

ID	Title	Description
OG000	DA + IV Iron	Patients receive darbepoetin alfa (DA) subcutaneously and sodium ferric gluconate complex intravenously (IV) over 90 minutes on day 1. Treatment repeats every 21 days for up to 15 weeks in the absence of unacceptable toxicity.
OG001	DA + Oral Iron	Patients receive darbepoetin alfa (DA) as in arm I and oral ferrous sulfate once daily on days 1-21. Treatment repeats every 21 days for up to 15 weeks in the absence of unacceptable toxicity.
OG002	DA + Placebo	Patients receive darbepoetin alfa (DA) as in arm I and oral placebo once daily on days 1-21. Treatment repeats every 21 days for up to 15 weeks in the absence of unacceptable toxicity.

Secondary

Time to First Red Blood Cell (RBC) Transfusions

Only 63 participants (20 DA + IV Iron, 21 DA + Oral Iron and 22 DA + Placebo) needed RBC transfusion during 16 weeks of treatment period. Thus, median of time to first RBC transfusion and 95 % confidence interval are not attainable.

Posted

Median

95% Confidence Interval

Days

16 weeks

ID	Title	Description
OG000	DA + IV Iron	Patients receive darbepoetin alfa (DA) subcutaneously and sodium ferric gluconate complex intravenously (IV) over 90 minutes on day 1. Treatment repeats every 21 days for up to 15 weeks in the absence of unacceptable toxicity.
OG001	DA + Oral Iron	Patients receive darbepoetin alfa (DA) as in arm I and oral ferrous sulfate once daily on days 1-21. Treatment repeats every 21 days for up to 15 weeks in the absence of unacceptable toxicity.
OG002	DA + Placebo	Patients receive darbepoetin alfa (DA) as in arm I and oral placebo once daily on days 1-21. Treatment repeats every 21 days for up to 15 weeks in the absence of unacceptable toxicity.

Secondary

Change From Baseline in Overall Quality of Life (QOL) Score as Measured by the Linear Analogue Self Assessment (LASA)

Overall QOL item score range: 0 (Worst) to 10 (Best), ordinal. Change: score at 16 weeks minus score at baseline.

Posted

Mean

Standard Deviation

Scores on a scale

Baseline and 16 weeks

ID	Title	Description
OG000	DA + IV Iron	Patients receive darbepoetin alfa (DA) subcutaneously and sodium ferric gluconate complex intravenously (IV) over 90 minutes on day 1. Treatment repeats every 21 days for up to 15 weeks in the absence of unacceptable toxicity.
OG001	DA + Oral Iron	Patients receive darbepoetin alfa (DA) as in arm I and oral ferrous sulfate once daily on days 1-21. Treatment repeats every 21 days for up to 15 weeks in the absence of unacceptable toxicity.
OG002	DA + Placebo	Patients receive darbepoetin alfa (DA) as in arm I and oral placebo once daily on days 1-21. Treatment repeats every 21 days for up to 15 weeks in the absence of unacceptable toxicity.

Units

Secondary

Change From Baseline in Quality of Life (QOL) Score as Measured by Symptom Distress Scale (SDS) at End of Study

SDS Scale range: 0 (Worst), 100 (Best), ordinal. Change: score at 16 weeks minus score at baseline. A clinically significant result will be defined as a shift of 10 points on a 0-100 point transformed scale between the average QOL scores of the 3 variants of iron therapy.

Posted

Mean

Standard Deviation

Scores on a scale

Baseline and 16 weeks

ID	Title	Description
OG000	DA + IV Iron	Patients receive darbepoetin alfa (DA) subcutaneously and sodium ferric gluconate complex intravenously (IV) over 90 minutes on day 1. Treatment repeats every 21 days for up to 15 weeks in the absence of unacceptable toxicity.
OG001	DA + Oral Iron	Patients receive darbepoetin alfa (DA) as in arm I and oral ferrous sulfate once daily on days 1-21. Treatment repeats every 21 days for up to 15 weeks in the absence of unacceptable toxicity.
OG002	DA + Placebo	Patients receive darbepoetin alfa (DA) as in arm I and oral placebo once daily on days 1-21. Treatment repeats every 21 days for up to 15 weeks in the absence of unacceptable toxicity.

Secondary

Change From Baseline in Quality of Life (QOL) Score as Measured by Brief Fatigue Inventory(BFI) Fatigue Now Scale at End of Study

Fatigue Now Scale range: 0 (No Fatigue) to 10 (Worst), ordinal. Change: score at 16 weeks minus score at baseline.

Posted

Mean

Standard Deviation

Scores on a scale

Baseline and 16 weeks

ID	Title	Description
OG000	DA + IV Iron	Patients receive darbepoetin alfa (DA) subcutaneously and sodium ferric gluconate complex intravenously (IV) over 90 minutes on day 1. Treatment repeats every 21 days for up to 15 weeks in the absence of unacceptable toxicity.
OG001	DA + Oral Iron	Patients receive darbepoetin alfa (DA) as in arm I and oral ferrous sulfate once daily on days 1-21. Treatment repeats every 21 days for up to 15 weeks in the absence of unacceptable toxicity.
OG002	DA + Placebo	Patients receive darbepoetin alfa (DA) as in arm I and oral placebo once daily on days 1-21. Treatment repeats every 21 days for up to 15 weeks in the absence of unacceptable toxicity.

Secondary

Change From Baseline in Quality of Life (QOL) Score as Measured by The Functional Assessment of Cancer Therapy-Anemia (FACT-An) at End of Study

FACT-AN Scale range: 0 (Worst) to 100 (Best), ordinal. Change: score at 16 weeks minus score at baseline. A clinically significant result will be defined as a shift of 10 points on a 0-100 point transformed scale between the average QOL scores of the 3 variants of iron therapy.

Posted

Mean

Standard Deviation

Scores on a scale

Baseline and 16 weeks

ID	Title	Description
OG000	DA + IV Iron	Patients receive darbepoetin alfa (DA) subcutaneously and sodium ferric gluconate complex intravenously (IV) over 90 minutes on day 1. Treatment repeats every 21 days for up to 15 weeks in the absence of unacceptable toxicity.
OG001	DA + Oral Iron	Patients receive darbepoetin alfa (DA) as in arm I and oral ferrous sulfate once daily on days 1-21. Treatment repeats every 21 days for up to 15 weeks in the absence of unacceptable toxicity.
OG002	DA + Placebo	Patients receive darbepoetin alfa (DA) as in arm I and oral placebo once daily on days 1-21. Treatment repeats every 21 days for up to 15 weeks in the absence of unacceptable toxicity.

Secondary

C-reactive Protein (CRP) Level at Week 1, Week 7 and Week 16

Posted

Mean

Standard Deviation

mg/L

1 Week, 7 Weeks and 16 Weeks

ID	Title	Description
OG000	DA + IV Iron	Patients receive darbepoetin alfa (DA) subcutaneously and sodium ferric gluconate complex intravenously (IV) over 90 minutes on day 1. Treatment repeats every 21 days for up to 15 weeks in the absence of unacceptable toxicity.
OG001	DA + Oral Iron	Patients receive darbepoetin alfa (DA) as in arm I and oral ferrous sulfate once daily on days 1-21. Treatment repeats every 21 days for up to 15 weeks in the absence of unacceptable toxicity.
OG002	DA + Placebo	Patients receive darbepoetin alfa (DA) as in arm I and oral placebo once daily on days 1-21. Treatment repeats every 21 days for up to 15 weeks in the absence of unacceptable toxicity.

Units	Counts
Participants

Secondary

Soluble Transferrin Receptor (sTfR)Level at Week 1, Week 7 and Week 16

Posted

Mean

Standard Deviation

mg/L

1 week, 7 weeks and 16 weeks

ID	Title	Description
OG000	DA + IV Iron	Patients receive darbepoetin alfa (DA) subcutaneously and sodium ferric gluconate complex intravenously (IV) over 90 minutes on day 1. Treatment repeats every 21 days for up to 15 weeks in the absence of unacceptable toxicity.
OG001	DA + Oral Iron	Patients receive darbepoetin alfa (DA) as in arm I and oral ferrous sulfate once daily on days 1-21. Treatment repeats every 21 days for up to 15 weeks in the absence of unacceptable toxicity.
OG002	DA + Placebo	Patients receive darbepoetin alfa (DA) as in arm I and oral placebo once daily on days 1-21. Treatment repeats every 21 days for up to 15 weeks in the absence of unacceptable toxicity.

Units	Counts
Participants

Secondary

Ferritin Level at Baseline, Week 7 and Week 16

Posted

Mean

Standard Deviation

µg/L

Baseline, 7 weeks and 16 weeks

ID	Title	Description
OG000	DA + IV Iron	Patients receive darbepoetin alfa (DA) subcutaneously and sodium ferric gluconate complex intravenously (IV) over 90 minutes on day 1. Treatment repeats every 21 days for up to 15 weeks in the absence of unacceptable toxicity.
OG001	DA + Oral Iron	Patients receive darbepoetin alfa (DA) as in arm I and oral ferrous sulfate once daily on days 1-21. Treatment repeats every 21 days for up to 15 weeks in the absence of unacceptable toxicity.
OG002	DA + Placebo	Patients receive darbepoetin alfa (DA) as in arm I and oral placebo once daily on days 1-21. Treatment repeats every 21 days for up to 15 weeks in the absence of unacceptable toxicity.

Units	Counts
Participants

Secondary

Mean Corpuscular Volume (MCV) Level at Baseline, Week 7 and Week 16

MCV is a measure of the average red blood cell volume.

Posted

Mean

Standard Deviation

Baseline, 7 weeks and 16 weeks

ID	Title	Description
OG000	DA + IV Iron	Patients receive darbepoetin alfa (DA) subcutaneously and sodium ferric gluconate complex intravenously (IV) over 90 minutes on day 1. Treatment repeats every 21 days for up to 15 weeks in the absence of unacceptable toxicity.
OG001	DA + Oral Iron	Patients receive darbepoetin alfa (DA) as in arm I and oral ferrous sulfate once daily on days 1-21. Treatment repeats every 21 days for up to 15 weeks in the absence of unacceptable toxicity.
OG002	DA + Placebo	Patients receive darbepoetin alfa (DA) as in arm I and oral placebo once daily on days 1-21. Treatment repeats every 21 days for up to 15 weeks in the absence of unacceptable toxicity.

Units	Counts
Participants

Secondary

Transferrin Saturation at Baseline, Week 7 and Week 16

Posted

Mean

Standard Deviation

Percentage Saturation

Baseline, 7 weeks and 16 weeks

ID	Title	Description
OG000	DA + IV Iron	Patients receive darbepoetin alfa (DA) subcutaneously and sodium ferric gluconate complex intravenously (IV) over 90 minutes on day 1. Treatment repeats every 21 days for up to 15 weeks in the absence of unacceptable toxicity.
OG001	DA + Oral Iron	Patients receive darbepoetin alfa (DA) as in arm I and oral ferrous sulfate once daily on days 1-21. Treatment repeats every 21 days for up to 15 weeks in the absence of unacceptable toxicity.
OG002	DA + Placebo	Patients receive darbepoetin alfa (DA) as in arm I and oral placebo once daily on days 1-21. Treatment repeats every 21 days for up to 15 weeks in the absence of unacceptable toxicity.

Units	Counts
Participants

Arm/Groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	DA + IV Iron	Patients receive darbepoetin alfa (DA) subcutaneously and sodium ferric gluconate complex intravenously (IV) over 90 minutes on day 1. Treatment repeats every 21 days for up to 15 weeks in the absence of unacceptable toxicity.	5	164	150	164
EG001	DA + Oral Iron	Patients receive darbepoetin alfa (DA) as in arm I and oral ferrous sulfate once daily on days 1-21. Treatment repeats every 21 days for up to 15 weeks in the absence of unacceptable toxicity.	3	163	147	163
EG002	DA + Placebo	Patients receive darbepoetin alfa (DA) as in arm I and oral placebo once daily on days 1-21. Treatment repeats every 21 days for up to 15 weeks in the absence of unacceptable toxicity.	2	163	141	163

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA 6	Systematic Assessment	EG0001 events1 affected164 at risk EG0010 events0 affected163 at risk EG0020 events0 affected163 at risk
Fistula-intestinal	Gastrointestinal disorders	MedDRA 6	Systematic Assessment	EG0000 events0 affected164 at risk EG0010 events0 affected163 at risk EG0021 events1 affected163 at risk
Fatigue	General disorders	MedDRA 6	Systematic Assessment	EG0000 events0 affected164 at risk EG0010 events0 affected163 at risk EG0021 events1 affected163 at risk
Syndromes	General disorders	MedDRA 6	Systematic Assessment	EG0001 events1 affected164 at risk EG0010 events0 affected163 at risk EG0020 events0 affected163 at risk
Pneumonia	Infections and infestations	MedDRA 6	Systematic Assessment	EG0001 events1 affected164 at risk EG0010 events0 affected163 at risk EG0020 events0 affected163 at risk
Activated partial thromboplastin time prolonged	Investigations	MedDRA 6	Systematic Assessment	EG0000 events0 affected164 at risk EG0011 events1 affected163 at risk EG0020 events0 affected163 at risk
Leukopenia	Investigations	MedDRA 6	Systematic Assessment	EG0000 events0 affected164 at risk EG0011 events1 affected163 at risk EG0020 events0 affected163 at risk
Neutropenia	Investigations	MedDRA 6	Systematic Assessment	EG0002 events2 affected164 at risk EG0010 events0 affected163 at risk EG0020 events0 affected163 at risk
Platelet count decreased	Investigations	MedDRA 6	Systematic Assessment	EG0001 events1 affected164 at risk EG0010 events0 affected163 at risk EG0020 events0 affected163 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 6	Systematic Assessment	EG0000 events0 affected164 at risk EG0011 events1 affected163 at risk EG0020 events0 affected163 at risk
Confusion	Psychiatric disorders	MedDRA 6	Systematic Assessment	EG0002 events1 affected164 at risk EG0010 events0 affected163 at risk EG0020 events0 affected163 at risk
Dyspnea	Respiratory, thoracic and mediastinal disorders	MedDRA 6	Systematic Assessment	EG0000 events0 affected164 at risk EG0012 events2 affected163 at risk EG0020 events0 affected163 at risk
Thrombosis	Vascular disorders	MedDRA 6	Systematic Assessment	EG0000 events0 affected164 at risk EG0011 events1 affected163 at risk EG0020 events0 affected163 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anemia	Blood and lymphatic system disorders	MedDRA 6	Systematic Assessment	EG0009 events6 affected164 at risk EG00114 events13 affected163 at risk EG0029 events8 affected163 at risk
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA 6	Systematic Assessment	EG0003 events3 affected164 at risk EG0011 events1 affected163 at risk EG0024 events2 affected163 at risk
Atrial fibrillation	Cardiac disorders	MedDRA 6	Systematic Assessment	EG0001 events1 affected164 at risk EG0010 events0 affected163 at risk EG0021 events1 affected163 at risk
Ischemia/Infarction	Cardiac disorders	MedDRA 6	Systematic Assessment	EG0000 events0 affected164 at risk EG0010 events0 affected163 at risk EG0021 events1 affected163 at risk
Pericardial effusion	Cardiac disorders	MedDRA 6	Systematic Assessment	EG0001 events1 affected164 at risk EG0010 events0 affected163 at risk EG0020 events0 affected163 at risk
Restrictive cardiomyopathy	Cardiac disorders	MedDRA 6	Systematic Assessment	EG0000 events0 affected164 at risk EG0010 events0 affected163 at risk EG0021 events1 affected163 at risk
Right ventricular dysfunction	Cardiac disorders	MedDRA 6	Systematic Assessment	EG0000 events0 affected164 at risk EG0010 events0 affected163 at risk EG0021 events1 affected163 at risk
Sinus tachycardia	Cardiac disorders	MedDRA 6	Systematic Assessment	EG0002 events2 affected164 at risk EG0010 events0 affected163 at risk EG0020 events0 affected163 at risk
Supraventricular tachycardia	Cardiac disorders	MedDRA 6	Systematic Assessment	EG0000 events0 affected164 at risk EG0010 events0 affected163 at risk EG0021 events1 affected163 at risk
Valvular heart disease	Cardiac disorders	MedDRA 6	Systematic Assessment	EG0000 events0 affected164 at risk EG0010 events0 affected163 at risk EG0021 events1 affected163 at risk
Extraocular muscle disorder	Eye disorders	MedDRA 6	Systematic Assessment	EG0000 events0 affected164 at risk EG0010 events0 affected163 at risk EG0021 events1 affected163 at risk
Ocular weakness	Eye disorders	MedDRA 6	Systematic Assessment	EG0001 events1 affected164 at risk EG0010 events0 affected163 at risk EG0020 events0 affected163 at risk
Vision-Blurred	Eye disorders	MedDRA 6	Systematic Assessment	EG0001 events1 affected164 at risk EG0010 events0 affected163 at risk EG0020 events0 affected163 at risk
Abdominal distension	Gastrointestinal disorders	MedDRA 6	Systematic Assessment	EG0000 events0 affected164 at risk EG0011 events1 affected163 at risk EG0020 events0 affected163 at risk
Anus Mucositis/stomatitis (clinical exam)	Gastrointestinal disorders	MedDRA 6	Systematic Assessment	EG0001 events1 affected164 at risk EG0010 events0 affected163 at risk EG0020 events0 affected163 at risk
Ascites	Gastrointestinal disorders	MedDRA 6	Systematic Assessment	EG0000 events0 affected164 at risk EG0011 events1 affected163 at risk EG0020 events0 affected163 at risk
Colonic hemorrhage	Gastrointestinal disorders	MedDRA 6	Systematic Assessment	EG0000 events0 affected164 at risk EG0011 events1 affected163 at risk EG0020 events0 affected163 at risk
Colonic perforation	Gastrointestinal disorders	MedDRA 6	Systematic Assessment	EG0001 events1 affected164 at risk EG0010 events0 affected163 at risk EG0020 events0 affected163 at risk
Constipation	Gastrointestinal disorders	MedDRA 6	Systematic Assessment	EG000163 events76 affected164 at risk EG001166 events72 affected163 at risk EG002182 events79 affected163 at risk
Diarrhea-No Colostom	Gastrointestinal disorders	MedDRA 6	Systematic Assessment	EG000131 events64 affected164 at risk EG001129 events64 affected163 at risk EG002131 events68 affected163 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA 6	Systematic Assessment	EG0004 events3 affected164 at risk EG0011 events1 affected163 at risk EG0021 events1 affected163 at risk
Dysphagia	Gastrointestinal disorders	MedDRA 6	Systematic Assessment	EG0002 events1 affected164 at risk EG0010 events0 affected163 at risk EG0020 events0 affected163 at risk
Flatulence	Gastrointestinal disorders	MedDRA 6	Systematic Assessment	EG0000 events0 affected164 at risk EG0010 events0 affected163 at risk EG0021 events1 affected163 at risk
Gastritis	Gastrointestinal disorders	MedDRA 6	Systematic Assessment	EG0001 events1 affected164 at risk EG0010 events0 affected163 at risk EG0020 events0 affected163 at risk
Gastrointestinal disorder	Gastrointestinal disorders	MedDRA 6	Systematic Assessment	EG0001 events1 affected164 at risk EG0010 events0 affected163 at risk EG0020 events0 affected163 at risk
Ileus	Gastrointestinal disorders	MedDRA 6	Systematic Assessment	EG0001 events1 affected164 at risk EG0010 events0 affected163 at risk EG0020 events0 affected163 at risk
Nausea	Gastrointestinal disorders	MedDRA 6	Systematic Assessment	EG000165 events76 affected164 at risk EG001164 events83 affected163 at risk EG002171 events82 affected163 at risk
Oral cavity Mucositis/stomatitis (functional/symptomatic)	Gastrointestinal disorders	MedDRA 6	Systematic Assessment	EG0000 events0 affected164 at risk EG0011 events1 affected163 at risk EG0022 events1 affected163 at risk
Pain-Abdominal	Gastrointestinal disorders	MedDRA 6	Systematic Assessment	EG0003 events3 affected164 at risk EG0015 events5 affected163 at risk EG0026 events6 affected163 at risk
Pain-Stomach	Gastrointestinal disorders	MedDRA 6	Systematic Assessment	EG0000 events0 affected164 at risk EG0010 events0 affected163 at risk EG0022 events1 affected163 at risk
Rectal hemorrhage	Gastrointestinal disorders	MedDRA 6	Systematic Assessment	EG0000 events0 affected164 at risk EG0011 events1 affected163 at risk EG0020 events0 affected163 at risk
Small intestinal obstruction	Gastrointestinal disorders	MedDRA 6	Systematic Assessment	EG0002 events2 affected164 at risk EG0010 events0 affected163 at risk EG0021 events1 affected163 at risk
Small intestinal stenosis	Gastrointestinal disorders	MedDRA 6	Systematic Assessment	EG0000 events0 affected164 at risk EG0010 events0 affected163 at risk EG0021 events1 affected163 at risk
Vomiting	Gastrointestinal disorders	MedDRA 6	Systematic Assessment	EG00069 events41 affected164 at risk EG00170 events37 affected163 at risk EG00257 events36 affected163 at risk
Disease Progression	General disorders	MedDRA 6	Systematic Assessment	EG0005 events5 affected164 at risk EG0014 events4 affected163 at risk EG0021 events1 affected163 at risk
Edema: Limb	General disorders	MedDRA 6	Systematic Assessment	EG0000 events0 affected164 at risk EG0012 events1 affected163 at risk EG0020 events0 affected163 at risk
Edema: Viscera	General disorders	MedDRA 6	Systematic Assessment	EG0000 events0 affected164 at risk EG0011 events1 affected163 at risk EG0020 events0 affected163 at risk
Fatigue	General disorders	MedDRA 6	Systematic Assessment	EG00032 events20 affected164 at risk EG00126 events17 affected163 at risk EG00227 events18 affected163 at risk
Multi-organ failure	General disorders	MedDRA 6	Systematic Assessment	EG0001 events1 affected164 at risk EG0010 events0 affected163 at risk EG0021 events1 affected163 at risk
Pain	General disorders	MedDRA 6	Systematic Assessment	EG0003 events3 affected164 at risk EG0010 events0 affected163 at risk EG0020 events0 affected163 at risk
Cholecystitis	Hepatobiliary disorders	MedDRA 6	Systematic Assessment	EG0000 events0 affected164 at risk EG0011 events1 affected163 at risk EG0020 events0 affected163 at risk
Cytokine release syndrome	Immune system disorders	MedDRA 6	Systematic Assessment	EG0001 events1 affected164 at risk EG0010 events0 affected163 at risk EG0021 events1 affected163 at risk
Hypersensitivity	Immune system disorders	MedDRA 6	Systematic Assessment	EG0001 events1 affected164 at risk EG0010 events0 affected163 at risk EG0020 events0 affected163 at risk
Abdominal infection	Infections and infestations	MedDRA 6	Systematic Assessment	EG0002 events2 affected164 at risk EG0010 events0 affected163 at risk EG0021 events1 affected163 at risk
Anal infection	Infections and infestations	MedDRA 6	Systematic Assessment	EG0001 events1 affected164 at risk EG0010 events0 affected163 at risk EG0020 events0 affected163 at risk
Bladder (urinary) infection	Infections and infestations	MedDRA 6	Systematic Assessment	EG0001 events1 affected164 at risk EG0011 events1 affected163 at risk EG0020 events0 affected163 at risk
Bladder infection	Infections and infestations	MedDRA 6	Systematic Assessment	EG0002 events2 affected164 at risk EG0010 events0 affected163 at risk EG0021 events1 affected163 at risk
Blood Infection	Infections and infestations	MedDRA 6	Systematic Assessment	EG0002 events2 affected164 at risk EG0010 events0 affected163 at risk EG0022 events2 affected163 at risk
Bronchus infection	Infections and infestations	MedDRA 6	Systematic Assessment	EG0001 events1 affected164 at risk EG0010 events0 affected163 at risk EG0020 events0 affected163 at risk
Colon infection	Infections and infestations	MedDRA 6	Systematic Assessment	EG0001 events1 affected164 at risk EG0010 events0 affected163 at risk EG0020 events0 affected163 at risk
Infection	Infections and infestations	MedDRA 6	Systematic Assessment	EG0000 events0 affected164 at risk EG0011 events1 affected163 at risk EG0021 events1 affected163 at risk
Lung (pneumonia) infection	Infections and infestations	MedDRA 6	Systematic Assessment	EG0001 events1 affected164 at risk EG0011 events1 affected163 at risk EG0022 events2 affected163 at risk
Pharyngitis	Infections and infestations	MedDRA 6	Systematic Assessment	EG0001 events1 affected164 at risk EG0010 events0 affected163 at risk EG0020 events0 affected163 at risk
Pneumonia	Infections and infestations	MedDRA 6	Systematic Assessment	EG0003 events3 affected164 at risk EG0013 events3 affected163 at risk EG0023 events3 affected163 at risk
Rectum infection	Infections and infestations	MedDRA 6	Systematic Assessment	EG0001 events1 affected164 at risk EG0010 events0 affected163 at risk EG0020 events0 affected163 at risk
Salivary gland infection	Infections and infestations	MedDRA 6	Systematic Assessment	EG0000 events0 affected164 at risk EG0010 events0 affected163 at risk EG0021 events1 affected163 at risk
Sepsis	Infections and infestations	MedDRA 6	Systematic Assessment	EG0001 events1 affected164 at risk EG0010 events0 affected163 at risk EG0020 events0 affected163 at risk
Skin (cellulites) infection	Infections and infestations	MedDRA 6	Systematic Assessment	EG0000 events0 affected164 at risk EG0011 events1 affected163 at risk EG0020 events0 affected163 at risk
Skin infection	Infections and infestations	MedDRA 6	Systematic Assessment	EG0005 events3 affected164 at risk EG0011 events1 affected163 at risk EG0024 events2 affected163 at risk
Upper airway infection	Infections and infestations	MedDRA 6	Systematic Assessment	EG0001 events1 affected164 at risk EG0010 events0 affected163 at risk EG0020 events0 affected163 at risk
Urinary tract infection	Infections and infestations	MedDRA 6	Systematic Assessment	EG0003 events3 affected164 at risk EG0012 events1 affected163 at risk EG0020 events0 affected163 at risk
Vaginal infection	Infections and infestations	MedDRA 6	Systematic Assessment	EG0000 events0 affected164 at risk EG0010 events0 affected163 at risk EG0021 events1 affected163 at risk
Fracture	Injury, poisoning and procedural complications	MedDRA 6	Systematic Assessment	EG0000 events0 affected164 at risk EG0010 events0 affected163 at risk EG0021 events1 affected163 at risk
Vascular access complication	Injury, poisoning and procedural complications	MedDRA 6	Systematic Assessment	EG0000 events0 affected164 at risk EG0010 events0 affected163 at risk EG0021 events1 affected163 at risk
Alanine aminotransferase increased	Investigations	MedDRA 6	Systematic Assessment	EG0001 events1 affected164 at risk EG0010 events0 affected163 at risk EG0022 events1 affected163 at risk
Alkaline phosphatase	Investigations	MedDRA 6	Systematic Assessment	EG0001 events1 affected164 at risk EG0011 events1 affected163 at risk EG0022 events2 affected163 at risk
Aspartate aminotransferase increased	Investigations	MedDRA 6	Systematic Assessment	EG0001 events1 affected164 at risk EG0011 events1 affected163 at risk EG0022 events2 affected163 at risk
Blood bilirubin increased	Investigations	MedDRA 6	Systematic Assessment	EG0002 events2 affected164 at risk EG0010 events0 affected163 at risk EG0023 events3 affected163 at risk
CPK (creatine phosphokinase)	Investigations	MedDRA 6	Systematic Assessment	EG0000 events0 affected164 at risk EG0010 events0 affected163 at risk EG0021 events1 affected163 at risk
Creatinine	Investigations	MedDRA 6	Systematic Assessment	EG0000 events0 affected164 at risk EG0014 events3 affected163 at risk EG0022 events2 affected163 at risk
Leukopenia	Investigations	MedDRA 6	Systematic Assessment	EG00019 events13 affected164 at risk EG00125 events17 affected163 at risk EG00252 events28 affected163 at risk
Lymphopenia	Investigations	MedDRA 6	Systematic Assessment	EG00016 events9 affected164 at risk EG00122 events11 affected163 at risk EG00222 events10 affected163 at risk
Neutropenia	Investigations	MedDRA 6	Systematic Assessment	EG00024 events17 affected164 at risk EG00121 events17 affected163 at risk EG00237 events21 affected163 at risk
Platelet count decreased	Investigations	MedDRA 6	Systematic Assessment	EG00013 events9 affected164 at risk EG00123 events15 affected163 at risk EG00224 events14 affected163 at risk
Prothrombin Time	Investigations	MedDRA 6	Systematic Assessment	EG0005 events2 affected164 at risk EG0010 events0 affected163 at risk EG0022 events2 affected163 at risk
Weight gain	Investigations	MedDRA 6	Systematic Assessment	EG0001 events1 affected164 at risk EG0010 events0 affected163 at risk EG0020 events0 affected163 at risk
Weight loss	Investigations	MedDRA 6	Systematic Assessment	EG0000 events0 affected164 at risk EG0012 events1 affected163 at risk EG0020 events0 affected163 at risk
Anorexia	Metabolism and nutrition disorders	MedDRA 6	Systematic Assessment	EG0006 events5 affected164 at risk EG0018 events3 affected163 at risk EG0023 events3 affected163 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA 6	Systematic Assessment	EG00012 events11 affected164 at risk EG0019 events8 affected163 at risk EG0027 events7 affected163 at risk
Hypercalcemia	Metabolism and nutrition disorders	MedDRA 6	Systematic Assessment	EG0001 events1 affected164 at risk EG0011 events1 affected163 at risk EG0020 events0 affected163 at risk
Hyperglycemia	Metabolism and nutrition disorders	MedDRA 6	Systematic Assessment	EG0003 events3 affected164 at risk EG00116 events10 affected163 at risk EG0027 events6 affected163 at risk
Hyperkalemia	Metabolism and nutrition disorders	MedDRA 6	Systematic Assessment	EG0000 events0 affected164 at risk EG0010 events0 affected163 at risk EG0022 events2 affected163 at risk
Hyperuricemia	Metabolism and nutrition disorders	MedDRA 6	Systematic Assessment	EG0000 events0 affected164 at risk EG0011 events1 affected163 at risk EG0020 events0 affected163 at risk
Hypoalbuminemia	Metabolism and nutrition disorders	MedDRA 6	Systematic Assessment	EG0001 events1 affected164 at risk EG0011 events1 affected163 at risk EG0023 events3 affected163 at risk
Hypocalcemia	Metabolism and nutrition disorders	MedDRA 6	Systematic Assessment	EG0003 events3 affected164 at risk EG0010 events0 affected163 at risk EG0021 events1 affected163 at risk
Hypoglycemia	Metabolism and nutrition disorders	MedDRA 6	Systematic Assessment	EG0001 events1 affected164 at risk EG0012 events2 affected163 at risk EG0020 events0 affected163 at risk
Hypokalemia	Metabolism and nutrition disorders	MedDRA 6	Systematic Assessment	EG0008 events7 affected164 at risk EG0014 events4 affected163 at risk EG0027 events5 affected163 at risk
Hypomagnesemia	Metabolism and nutrition disorders	MedDRA 6	Systematic Assessment	EG0001 events1 affected164 at risk EG0010 events0 affected163 at risk EG0021 events1 affected163 at risk
Hyponatremia	Metabolism and nutrition disorders	MedDRA 6	Systematic Assessment	EG0005 events5 affected164 at risk EG0014 events3 affected163 at risk EG0026 events4 affected163 at risk
Iron increased	Metabolism and nutrition disorders	MedDRA 6	Systematic Assessment	EG0000 events0 affected164 at risk EG0011 events1 affected163 at risk EG0020 events0 affected163 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 6	Systematic Assessment	EG0000 events0 affected164 at risk EG0010 events0 affected163 at risk EG0021 events1 affected163 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 6	Systematic Assessment	EG0005 events5 affected164 at risk EG0014 events2 affected163 at risk EG0020 events0 affected163 at risk
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA 6	Systematic Assessment	EG0002 events2 affected164 at risk EG0015 events3 affected163 at risk EG0022 events2 affected163 at risk
Chest wall pain	Musculoskeletal and connective tissue disorders	MedDRA 6	Systematic Assessment	EG0001 events1 affected164 at risk EG0010 events0 affected163 at risk EG0020 events0 affected163 at risk
Extremity-lower weakness	Musculoskeletal and connective tissue disorders	MedDRA 6	Systematic Assessment	EG0000 events0 affected164 at risk EG0010 events0 affected163 at risk EG0021 events1 affected163 at risk
Muscle Weakness	Musculoskeletal and connective tissue disorders	MedDRA 6	Systematic Assessment	EG0005 events4 affected164 at risk EG0012 events2 affected163 at risk EG0022 events2 affected163 at risk
Musculoskeletal	Musculoskeletal and connective tissue disorders	MedDRA 6	Systematic Assessment	EG0000 events0 affected164 at risk EG0011 events1 affected163 at risk EG0021 events1 affected163 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 6	Systematic Assessment	EG0001 events1 affected164 at risk EG0011 events1 affected163 at risk EG0021 events1 affected163 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 6	Systematic Assessment	EG0001 events1 affected164 at risk EG0010 events0 affected163 at risk EG0022 events1 affected163 at risk
Trunk weakness	Musculoskeletal and connective tissue disorders	MedDRA 6	Systematic Assessment	EG0000 events0 affected164 at risk EG0010 events0 affected163 at risk EG0021 events1 affected163 at risk
Pain-Anal	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 6	Systematic Assessment	EG0000 events0 affected164 at risk EG0010 events0 affected163 at risk EG0021 events1 affected163 at risk
Depressed level of consciousness	Nervous system disorders	MedDRA 6	Systematic Assessment	EG0000 events0 affected164 at risk EG0010 events0 affected163 at risk EG0021 events1 affected163 at risk
Dizziness	Nervous system disorders	MedDRA 6	Systematic Assessment	EG0001 events1 affected164 at risk EG0013 events3 affected163 at risk EG0022 events2 affected163 at risk
Dysgeusia	Nervous system disorders	MedDRA 6	Systematic Assessment	EG0001 events1 affected164 at risk EG0011 events1 affected163 at risk EG0020 events0 affected163 at risk
Ischemia-Cerebral	Nervous system disorders	MedDRA 6	Systematic Assessment	EG0001 events1 affected164 at risk EG0011 events1 affected163 at risk EG0020 events0 affected163 at risk
Mental status changes	Nervous system disorders	MedDRA 6	Systematic Assessment	EG0001 events1 affected164 at risk EG0010 events0 affected163 at risk EG0020 events0 affected163 at risk
Neuralgia	Nervous system disorders	MedDRA 6	Systematic Assessment	EG0003 events2 affected164 at risk EG0010 events0 affected163 at risk EG0020 events0 affected163 at risk
Neuro	Nervous system disorders	MedDRA 6	Systematic Assessment	EG0000 events0 affected164 at risk EG0011 events1 affected163 at risk EG0020 events0 affected163 at risk
Peripheral motor neuropathy	Nervous system disorders	MedDRA 6	Systematic Assessment	EG0001 events1 affected164 at risk EG0012 events2 affected163 at risk EG0020 events0 affected163 at risk
Peripheral sensory neuropathy	Nervous system disorders	MedDRA 6	Systematic Assessment	EG0008 events5 affected164 at risk EG0012 events2 affected163 at risk EG0026 events4 affected163 at risk
Seizure	Nervous system disorders	MedDRA 6	Systematic Assessment	EG0001 events1 affected164 at risk EG0010 events0 affected163 at risk EG0020 events0 affected163 at risk
Syncope	Nervous system disorders	MedDRA 6	Systematic Assessment	EG0004 events4 affected164 at risk EG0011 events1 affected163 at risk EG0023 events3 affected163 at risk
Syncope Vasovagal	Nervous system disorders	MedDRA 6	Systematic Assessment	EG0001 events1 affected164 at risk EG0010 events0 affected163 at risk EG0020 events0 affected163 at risk
Tremor	Nervous system disorders	MedDRA 6	Systematic Assessment	EG0000 events0 affected164 at risk EG0010 events0 affected163 at risk EG0021 events1 affected163 at risk
Anxiety	Psychiatric disorders	MedDRA 6	Systematic Assessment	EG0001 events1 affected164 at risk EG0010 events0 affected163 at risk EG0020 events0 affected163 at risk
Confusion	Psychiatric disorders	MedDRA 6	Systematic Assessment	EG0000 events0 affected164 at risk EG0010 events0 affected163 at risk EG0021 events1 affected163 at risk
Insomnia	Psychiatric disorders	MedDRA 6	Systematic Assessment	EG0000 events0 affected164 at risk EG0010 events0 affected163 at risk EG0022 events2 affected163 at risk
Glomerular filtration rate	Renal and urinary disorders	MedDRA 6	Systematic Assessment	EG0000 events0 affected164 at risk EG0010 events0 affected163 at risk EG0021 events1 affected163 at risk
Renal Failure	Renal and urinary disorders	MedDRA 6	Systematic Assessment	EG0000 events0 affected164 at risk EG0012 events1 affected163 at risk EG0020 events0 affected163 at risk
Pelvic pain	Reproductive system and breast disorders	MedDRA 6	Systematic Assessment	EG0001 events1 affected164 at risk EG0010 events0 affected163 at risk EG0020 events0 affected163 at risk
Vaginal fistula	Reproductive system and breast disorders	MedDRA 6	Systematic Assessment	EG0000 events0 affected164 at risk EG0010 events0 affected163 at risk EG0021 events1 affected163 at risk
Adult respiratory distress syndrome (ARDS)	Respiratory, thoracic and mediastinal disorders	MedDRA 6	Systematic Assessment	EG0001 events1 affected164 at risk EG0010 events0 affected163 at risk EG0020 events0 affected163 at risk
Atelectasis	Respiratory, thoracic and mediastinal disorders	MedDRA 6	Systematic Assessment	EG0001 events1 affected164 at risk EG0010 events0 affected163 at risk EG0020 events0 affected163 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 6	Systematic Assessment	EG0000 events0 affected164 at risk EG0011 events1 affected163 at risk EG0022 events2 affected163 at risk
Dyspnea	Respiratory, thoracic and mediastinal disorders	MedDRA 6	Systematic Assessment	EG00021 events13 affected164 at risk EG0019 events8 affected163 at risk EG00219 events16 affected163 at risk
Hypoxia	Respiratory, thoracic and mediastinal disorders	MedDRA 6	Systematic Assessment	EG0005 events3 affected164 at risk EG0012 events2 affected163 at risk EG0023 events3 affected163 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA 6	Systematic Assessment	EG0000 events0 affected164 at risk EG0011 events1 affected163 at risk EG0022 events2 affected163 at risk
Pulmonary	Respiratory, thoracic and mediastinal disorders	MedDRA 6	Systematic Assessment	EG0001 events1 affected164 at risk EG0010 events0 affected163 at risk EG0020 events0 affected163 at risk
Pulmonary hypertension	Respiratory, thoracic and mediastinal disorders	MedDRA 6	Systematic Assessment	EG0000 events0 affected164 at risk EG0011 events1 affected163 at risk EG0021 events1 affected163 at risk
Acne	Skin and subcutaneous tissue disorders	MedDRA 6	Systematic Assessment	EG0000 events0 affected164 at risk EG0012 events1 affected163 at risk EG0020 events0 affected163 at risk
Hand-foot skin reaction	Skin and subcutaneous tissue disorders	MedDRA 6	Systematic Assessment	EG0000 events0 affected164 at risk EG0010 events0 affected163 at risk EG0024 events2 affected163 at risk
Pain of skin	Skin and subcutaneous tissue disorders	MedDRA 6	Systematic Assessment	EG0002 events1 affected164 at risk EG0010 events0 affected163 at risk EG0020 events0 affected163 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 6	Systematic Assessment	EG00077 events44 affected164 at risk EG00191 events48 affected163 at risk EG00277 events46 affected163 at risk
Rash/Desquamation	Skin and subcutaneous tissue disorders	MedDRA 6	Systematic Assessment	EG0001 events1 affected164 at risk EG0010 events0 affected163 at risk EG0020 events0 affected163 at risk
Sweating	Skin and subcutaneous tissue disorders	MedDRA 6	Systematic Assessment	EG0000 events0 affected164 at risk EG0010 events0 affected163 at risk EG0021 events1 affected163 at risk
Urticaria	Skin and subcutaneous tissue disorders	MedDRA 6	Systematic Assessment	EG0001 events1 affected164 at risk EG0010 events0 affected163 at risk EG0020 events0 affected163 at risk
Flushing	Vascular disorders	MedDRA 6	Systematic Assessment	EG00066 events34 affected164 at risk EG00155 events30 affected163 at risk EG00258 events33 affected163 at risk
Hypertension	Vascular disorders	MedDRA 6	Systematic Assessment	EG00028 events17 affected164 at risk EG00129 events20 affected163 at risk EG00216 events14 affected163 at risk
Hypotension	Vascular disorders	MedDRA 6	Systematic Assessment	EG00034 events23 affected164 at risk EG00119 events13 affected163 at risk EG00231 events24 affected163 at risk
Phlebitis	Vascular disorders	MedDRA 6	Systematic Assessment	EG0000 events0 affected164 at risk EG0010 events0 affected163 at risk EG0021 events1 affected163 at risk
Thrombosis	Vascular disorders	MedDRA 6	Systematic Assessment	EG0007 events7 affected164 at risk EG0010 events0 affected163 at risk EG0028 events8 affected163 at risk

ID	Term
D000740	Anemia
D007938	Leukemia
D008223	Lymphoma
D008232	Lymphoproliferative Disorders
D009101	Multiple Myeloma
D054219	Neoplasms, Plasma Cell
D011230	Precancerous Conditions
D008998	Monoclonal Gammopathy of Undetermined Significance
D000075363	Immunoglobulin Light-chain Amyloidosis
D008258	Waldenstrom Macroglobulinemia
D054218	Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
D007119	Immunoblastic Lymphadenopathy
D017728	Lymphoma, Large-Cell, Anaplastic
D016410	Lymphoma, T-Cell, Cutaneous
D009182	Mycosis Fungoides
D012751	Sezary Syndrome
D006689	Hodgkin Disease
D002051	Burkitt Lymphoma
D016403	Lymphoma, Large B-Cell, Diffuse
D008228	Lymphoma, Non-Hodgkin
D016400	Lymphoma, Large-Cell, Immunoblastic
D054198	Precursor Cell Lymphoblastic Leukemia-Lymphoma
D008224	Lymphoma, Follicular
D020522	Lymphoma, Mantle-Cell
D018442	Lymphoma, B-Cell, Marginal Zone
D015451	Leukemia, Lymphocytic, Chronic, B-Cell
D007943	Leukemia, Hairy Cell
D015463	Leukemia, Prolymphocytic
D054066	Leukemia, Large Granular Lymphocytic
D015456	Leukemia, Biphenotypic, Acute
D007946	Leukemia, Mast-Cell
D054391	Lymphoma, Extranodal NK-T-Cell

Ancestor Terms

ID	Term
D006402	Hematologic Diseases
D006425	Hemic and Lymphatic Diseases
D009370	Neoplasms by Histologic Type
D009369	Neoplasms
D008206	Lymphatic Diseases
D007160	Immunoproliferative Disorders
D007154	Immune System Diseases
D020141	Hemostatic Disorders
D014652	Vascular Diseases
D002318	Cardiovascular Diseases
D010265	Paraproteinemias
D001796	Blood Protein Disorders
D006474	Hemorrhagic Disorders
D006942	Hypergammaglobulinemia
D000686	Amyloidosis
D057165	Proteostasis Deficiencies
D008659	Metabolic Diseases
D009750	Nutritional and Metabolic Diseases
D007945	Leukemia, Lymphoid
D000072281	Lymphadenopathy
D016399	Lymphoma, T-Cell
D020031	Epstein-Barr Virus Infections
D006566	Herpesviridae Infections
D004266	DNA Virus Infections
D014777	Virus Diseases
D007239	Infections
D014412	Tumor Virus Infections
D016393	Lymphoma, B-Cell
D015448	Leukemia, B-Cell
D002908	Chronic Disease
D020969	Disease Attributes
D010335	Pathologic Processes
D013568	Pathological Conditions, Signs and Symptoms
D015458	Leukemia, T-Cell
D015470	Leukemia, Myeloid, Acute
D007951	Leukemia, Myeloid
D034721	Mastocytosis, Systemic
D008415	Mastocytosis
D000090362	Mast Cell Activation Disorders

ID	Term
D000068256	Darbepoetin alfa
C020748	ferrous sulfate
C035552	ferric gluconate
D013395	Sucrose

ID	Term
D004921	Erythropoietin
D003115	Colony-Stimulating Factors
D006023	Glycoproteins
D006001	Glycoconjugates
D002241	Carbohydrates
D011506	Proteins
D000602	Amino Acids, Peptides, and Proteins
D004187	Disaccharides
D009844	Oligosaccharides
D011134	Polysaccharides
D000073893	Sugars