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.
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.
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.
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.
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:

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

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

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

 4. 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.