STAAR-2 Clinical Study

A Multicenter Study Using Once Every Other Week Subcutaneous Administration of Aranesp™ (Darbepoetin Alfa) and Iron Guided Algorithms to Treat Subjects With Anemia of Chronic Renal Insufficiency (CRI)

To assess the effect of Aranesp on the hemoglobin (Hgb) of CRI subjects who are recombinant human erythropoietin (rHuEPO)-naïve or converting from rHuEPO therapy.

To assess the effect of Aranesp_ on the hemoglobin (Hgb) of CRI subjects who are recombinant human erythropoietin (rHuEPO)-naïve or converting from rHuEPO therapy. To assess the association between subject self-reported health-related quality of life (HRQoL) as it relates to Hgb concentration and glomerular filtration rate (GFR) in subjects who were rHuEPO-naïve prior to study enrollment. To characterize the health-related resource utilization of subjects with CRI. To characterize the subject satisfaction with Aranesp_ compared to previous rHuEPO therapy. To characterize iron treatment in subjects with CRI. To assess the safety profile of Aranesp_ therapy in subjects with CRI

Inclusion Criteria:

• ≥ 18 years old
• diagnosis of CRI and not receiving dialysis therapy (must be predialysis)
• measured or estimated (using the Cockcroft-Gault formula) creatinine clearance (CrCl) of ≤ 70 mL/min, or GFR ≤ 60 mL/min (using the MDRD formula):
• Cockcroft-Gault formula: CrCl = (140 minus age in years) x (body weight in kg) serum creatinine (mg/dL) x 72.0 For women, the value will be multiplied by 0.85
• MDRD formula: GFR = 170 x [SCr]-0.999 x [Age]-0.167 x [0.762 if subject is female] x [1.180 if subject is black] x [sun] -0.170SAlb]-0.318
• mean Hgb < 11 g/dL during the screening/baseline period (if subject is not already receiving rHuEPO therapy)
• for subjects currently receiving rHuEPO therapy, the subject must have: a stable rHuEPO dose for the past month; and a rHuEPO frequency of once weekly.
• white blood cell and platelet counts within normal limits
• serum vitamin B12 and folate levels above the lower limit of normal range
• transferrin saturation (TSAT) ≥ 20% during the screening period
• availability for follow-up assessments
• subject must be able to comprehend and be willing to, or have legally accepted representative, give written informed consent for participation in the study

Exclusion Criteria:

• scheduled to initiate dialysis
• uncontrolled hypertension (diastolic blood pressure > 105 mm Hg or systolic blood pressure of > 180 mm Hg during the screening/baseline period on two separate measurements)
• clinically unstable in the judgment of the investigator (eg, subject is in the intensive care unit, immediately post-myocardial infarction, etc)
• scheduled to receive a living donor kidney transplant
• treatment of grand mal epilepsy within the past 6 months
• moderate to severe congestive heart failure (NYHA class III or IV)
• clinical evidence of severe secondary hyperparathyroidism (parathyroid hormone level > 1500 pg/mL)
• severe active chronic inflammatory process (eg, ulcerative colitis, peptic ulcer disease, rheumatoid arthritis, etc)
• currently receiving antibiotic therapy for systemic infection (enrollment may be postponed until the course of antibiotics has ended)
• known aspartate aminotransferase (AST) or alanine aminotransferase (ALT) greater than 3 times the upper limit of the normal range on more than one occasion within three months prior to screening
• known positive HIV antibody or hepatitis B surface antigen
• clinical evidence of current malignancy and/or receiving chemotherapy with the exception of basal cell or squamous cell carcinoma of the skin and cervical intraepithelial neoplasia
• active bleeding or RBC transfusion within eight weeks of enrollment
• androgen therapy within four weeks before enrollment
• known hematologic disease (eg, sickle cell anemia, myelodysplastic syndromes, hematologic malignancy, myeloma; hemolytic anemia, etc)
• any condition that is likely to affect subject compliance
• currently or previously (within 30 days) enrolled in investigational device or drug trial(s) or receiving investigational agent(s)
• the exception to this is if the subject was enrolled in another Aranesp™ or rHuEPO protocol
• pregnant or breast feeding women (women of child-bearing potential must be using contraceptive precautions)
• women planning to have a child during the study period
• known hypersensitivity to the active substance or any of the excipients