A Study Comparing the Effects of Epoetin Hospira and Epoetin Alpha (Amgen) When Administered IV in Patients With Chronic Renal Failure Requiring Hemodialysis and Receiving Epoetin Maintenance Treatment

This study will assess the pharmacokinetics (PK) of epoetin from Epoetin Hospira and Epogen in patients with renal failure receiving hemodialysis treatment.

This is a multicenter, active-controlled, cross-over, evaluator-blind, Phase I study in patients with chronic renal failure requiring hemodialysis. The study comprises a 4-week Screening Period, a 1-week Pre-Treatment Period, a 1-week Treatment Period 1, a 1-week Treatment Period 2 and a Follow-up visit at Week 7.

Subject eligibility will be determined during the 4-week Screening Period. All subjects must be optimally titrated and stable to qualify for entry into Pre-Treatment Period.

During the 1-week Pre-treatment period the patients will continue on the same stable dose as they received during the Screening Period. Blood samples will be collected during the Pre-Treatment Period to assess pharmacokinetics of Epogen. Eligible subjects will be randomized at Day 1 of Treatment Period 1 to receive either Epoetin Hospira or Epogen (Amgen) by intravenous (IV) bolus injections administered three times a week for 1 week.

Subjects will then be switched to receive the alternate study drug for three times a week for 1 week in Treatment Period 2. Blood samples will be collected during Treatment periods 1 and 2 to assess pharmacokinetics of Epoetin Hospira and Epogen.

Primary endpoint, i.e. pharmacokinetics concentrations, will be evaluator blinded. After completing Treatment Period 2, all subjects will receive standard of care treatment and will undergo a Follow-up Visit at Week 7 (i.e., 28 days after Treatment Period 2).

• Drug: Epoetin Hospira
  IV dose 3 times a week.
• Drug: Epogen
  IV dose 3 times a week

• Experimental: Arm A: Epoetin Hospira administered IV for three doses
  Intervention: Drug: Epoetin Hospira
• Active Comparator: Arm B: Epogen administered IV for three doses
  Intervention: Drug: Epogen

Inclusion Criteria:

• Able to provide written informed consent after risks and benefits of the study have been explained prior to any study related activities.
• Males and females between 18 and 75 years of age (both inclusive).

• Hemodialysis patients with chronic renal failure and anemia currently on stable epoetin treatment for at least 4 weeks prior to the Day 1 of Pre-treatment where during this period:

  • Epoetin alpha dose has been administered IV, 3 times a week and where each dose is <= 200 International Units(IU)/KG.
  • Hb levels were maintained within the 10-12 g/dL, with no more than a 0.5 g/dL change from the mean over this period.
  • No dose change during the last 4 weeks prior to Day 1 of pre-treatment period.
• Subjects on stable, adequate dialysis for at least 12 weeks prior to randomization, defined as no clinically relevant changes of dialysis regimen and/or dialyzer.
• subjects with adequate iron stones, defined as serum ferritin >= 100 ug/L and ISAT >20% prior to randomization.

• If female, subject must be postmenopausal for at lest 1 year prior to randomization, surgically sterile (bilateral tubal ligation, bilateral oophorectomy or hysterectomy), or practicing at least one of the following forms of birth control:

  • hormonal contraceptives (oral, parenteral or transdermal) for at least 3 months prior to randomization.
  • intrauterine device (IUD)
  • double-barrier method (condoms, contraceptive sponge, diaphragm or vaginal ring with spermicidal jellies or cream).

Exclusion Criteria:

• A subject with any active, uncontrolled systemic disease, including but not limited to microbial, viral or fungal infection or mental disease (including demyelinating diseases such as multiple sclerosis).
• History of drug abuse or alcohol abuse within 2 years prior to randomization as determined by the Investigator or a positive serum or saliva drug screen during the Screening Period or on Day 1 of Treatment Period.
• Significant drug sensitivity or a significant allergic reaction to any drug, as well as known hypersensitivity or idiosyncratic reaction to epoetin (or it's excipients, including albumin) or any other related drugs.
• A subject who in the Investigator's opinion, has any clinically significant abnormal laboratory evaluations, including Human Immunodeficiency Virus (HIV), Hepatitis B virus surface antigen (HBsAg) and liver function taken at Screening Visit.
• Current treatment with long-acting epoetin analogues such as Aranesp.
• The following within 6 months prior to randomization: unstable congestive heart failure (New York Heart Association [NYHA] class II or IV), cerebrovascular accident, myocardial infarction, coronary angioplasty or by-pass surgery.
• Uncontrolled hypertension in Investigator's opinion within 4 weeks prior to randomization.
• A subject who has received a recent (within last 6 months) live or attenuated vaccination.
• A female subject who is pregnant, nursing, or planning a pregnancy during the study.
• Donated or lost >= 457 ml (i.e., 1 pint) blood volume (including plasmapheresis) or had a transfusion of any blood product within 3 months prior to randomization.
• Known clinically manifested untreated deficiency of folic acid and/or vitamin B12.
• Current participation or participation in a drug or other investigational research study within 30 days prior to randomization.
• May not be able to comply with the requirements of this clinical trial, communicate effectively with study personnel, or is considered by the Investigator, for any reason, to be an unsuitable candidate for the study.
• Known positive test for anti-epoetin antibodies.