4 Week Switch Study in Hemodialysis-dependent Subjects With Anemia Associated With Chronic Kidney Disease

Inclusion Criteria

• Age and weight: >/=18 years of age and >/=45 kg (weight post-dialysis).
• On three times weekly hemodialysis for at least 8 weeks, irrespective of eGFR values and stage of chronic kidney disease (CKD).
• A single-pool Kt/Vurea of >/=1.2 based on a historical value obtained within the prior month in order to ensure the adequacy of dialysis. If Kt/Vurea is not available, then an average of the last 2 values of urea reduction ratio (URR) of at least 65%.
• rhEPO use: Using the same rhEPO (epoetins or darbepoetin) with total weekly doses that varied by no more than 50% during the prior 4 weeks (i.e., maximum vs. minimum total weekly doses /= 2.0 ng/mL (may rescreen in one month).
• Ferritin: >/=40 ng/mL with the absence of microcytic or hypochromic RBCs.
• Transferrin saturation (TSAT): Within the reference range.
• Iron replacement therapy: Stable maintenance dose of oral iron replacement therapy, if required, that will be maintained throughout the study. NOTE: IV iron replacement therapy is not allowed the two weeks prior to Screening through the end of the study (Week 6).
• QTc: QTcB 40MIU/ml and estradiol /=360 IU/kg/week IV or darbepoetin dose of >/=1.8 µg/kg/week IV within the prior 8 weeks.
• Renal transplant: Renal transplant anticipated or scheduled within the study time period or subjects with a functioning renal transplant.
• Mircera or Peginesatide: Current or prior use (within the prior 8 weeks) of Mircera (methoxy polyethylene glycol epoetin beta) OR peginesatide.
• Total CPK: >5x the upper limit of the reference range.
• HIV: Positive HIV antibody.
• History of myocardial infarction or acute coronary syndrome within the prior 6 months.
• History of stroke or transient ischemic attacks (TIAs) within the prior 6 months.
• Heart failure: Class III/IV heart failure, as defined by the New York Heart Association (NYHA) functional classification system.
• Hypertension: Poorly controlled hypertension, whether due to inadequate treatment, or lack of treatment, is defined as follows:
• DBP >100 mmHg or SBP>160 mmHg for subjects taking hypertension medication(s) before screening and dialysis, if required.
• DBP >105 mmHg or SBP>170 mmHg for subjects who are asked to hold hypertension medication(s) before screening and dialysis.
• Thrombotic Disease: History of thrombotic disease (e.g., venous thrombosis such as deep vein thrombosis or pulmonary embolism, or arterial thrombosis such as new onset or worsening limb ischemia requiring intervention), or other thrombosis related condition except shunt thrombosis) within the prior 6 months.
• Pulmonary hypertension: Known pulmonary hypertension and those at higher risk (than normally associated with CKD) for pre-existing elevation in pulmonary pressure (e.g., significant heart failure or lung disease requiring supplemental oxygen, or those with connective tissue diseases).
• Inflammatory disease: Chronic inflammatory disease that could impact erythropoiesis (e.g., scleroderma, systemic lupus erythematosis, rheumatoid arthritis, celiac disease).
• Haematological disease: Any haematological disease including those affecting platelets, the coagulation disorders (e.g., Protein C or S deficiency) or red blood cells (e.g. sickle cell anemia, myelodysplastic syndromes, haematological malignancy, myeloma, haemolytic anemia) or any other cause of anemia other than renal disease.
• Liver disease: Current liver disease, known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones) or evidence at Screening of abnormal liver function tests [alkaline phosphatase, alanine transaminase (ALT) or aspartate transaminase (AST) > 2.0 x upper limit of normal (ULN) or total bilirubin > 1.5 x ULN]; or other hepatic abnormalities that in the opinion of the investigator would preclude the subject from participation in the study.
• Major surgery: (excluding vascular access surgery) Within the prior 12 weeks or