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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hospira, Inc.
ClinicalTrials.gov Identifier:
NCT01170078
First received: July 23, 2010
Last updated: June 12, 2015
Last verified: June 2015
  Purpose

This study assessed the comparability of the pharmacokinetics (PK) of epoetin following intravenous administration of Hospira Epoetin and Epogen/Epoetin Alfa (Amgen) in patients with chronic renal failure receiving hemodialysis treatment.


Condition Intervention Phase
Chronic Renal Failure
Drug: Epoetin Hospira
Drug: Epogen
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Bio-equivalence Study
Intervention Model: Crossover Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 1 Study Comparing the Pharmacokinetics of Epoetin Hospira and Epoetin Alfa (Amgen) When Administered Intravenously in Patients With Chronic Renal Failure Requiring Hemodialysis and Receiving Epoetin Maintenance Treatment

Resource links provided by NLM:


Further study details as provided by Hospira, Inc.:

Primary Outcome Measures:
  • Baseline-adjusted area under the serum epoetin concentration curve from the time of dose administration to 48 hours (AUC0-48) [ Time Frame: On Day 1 and 2 of Pre-Treatment and Treatment Periods 1 and 2 predose (0 hour). On Day 3 of Pre-Treatment Period and Treatment Periods 1 and 2 (i.e., 3rd epoetin dose of the week) at predose (0 hour) and postdose (0.5, 1, 2, 4, 6, 8, 12, 24 and 48 hours) ] [ Designated as safety issue: No ]
  • Maximum serum epoetin concentration (Cmax) [ Time Frame: On Day 1 and 2 of Pre-Treatment and Treatment Periods 1 and 2 predose (0 hour). On Day 3 of Pre-Treatment Period and Treatment Periods 1 and 2 (i.e., 3rd epoetin dose of the week) at predose (0 hour) and postdose (0.5, 1, 2, 4, 6, 8, 12, 24 and 48 hours) ] [ Designated as safety issue: No ]
  • AUC from time of dose administration to the time of the last measurable concentration (AUC0-t) [ Time Frame: On Day 1 and 2 of Pre-Treatment and Treatment Periods 1 and 2 predose (0 hour). On Day 3 of Pre-Treatment Period and Treatment Periods 1 and 2 (i.e., 3rd epoetin dose of the week) at predose (0 hour) and postdose (0.5, 1, 2, 4, 6, 8, 12, 24 and 48 hours) ] [ Designated as safety issue: No ]
    If AUC0-48 cannot be calculated then AUC from time of dose administration to the time of the last measurable concentration (AUC0-t) will be used as the primary measure.


Secondary Outcome Measures:
  • Dose-adjusted Cmax [ Time Frame: On Day 1 and 2 of Pre-Treatment and Treatment Periods 1 and 2 predose (0 hour). On Day 3 of Pre-Treatment Period and Treatment Periods 1 and 2 (i.e., 3rd epoetin dose of the week) at predose (0 hour) and postdose (0.5, 1, 2, 4, 6, 8, 12, 24 and 48 hours) ] [ Designated as safety issue: No ]
  • AUC from time of dose administration to the time of the last measurable concentration (AUC0-t) [ Time Frame: On Day 1 and 2 of Pre-Treatment and Treatment Periods 1 and 2 predose (0 hour). On Day 3 of Pre-Treatment Period and Treatment Periods 1 and 2 (i.e., 3rd epoetin dose of the week) at predose (0 hour) and postdose (0.5, 1, 2, 4, 6, 8, 12, 24 and 48 hours) ] [ Designated as safety issue: No ]
  • Elimination rate Constant (λz) [ Time Frame: On Day 1 and 2 of Pre-Treatment and Treatment Periods 1 and 2 predose (0 hour). On Day 3 of Pre-Treatment Period and Treatment Periods 1 and 2 (i.e., 3rd epoetin dose of the week) at predose (0 hour) and postdose (0.5, 1, 2, 4, 6, 8, 12, 24 and 48 hours) ] [ Designated as safety issue: No ]
  • Elimination halflife (t1/2) [ Time Frame: On Day 1 and 2 of Pre-Treatment and Treatment Periods 1 and 2 predose (0 hour). On Day 3 of Pre-Treatment Period and Treatment Periods 1 and 2 (i.e., 3rd epoetin dose of the week) at predose (0 hour) and postdose (0.5, 1, 2, 4, 6, 8, 12, 24 and 48 hours) ] [ Designated as safety issue: No ]
  • Clearance (CL) [ Time Frame: On Day 1 and 2 of Pre-Treatment and Treatment Periods 1 and 2 predose (0 hour). On Day 3 of Pre-Treatment Period and Treatment Periods 1 and 2 (i.e., 3rd epoetin dose of the week) at predose (0 hour) and postdose (0.5, 1, 2, 4, 6, 8, 12, 24 and 48 hours) ] [ Designated as safety issue: No ]
  • Volume of Distribution (Vd) [ Time Frame: On Day 1 and 2 of Pre-Treatment and Treatment Periods 1 and 2 predose (0 hour). On Day 3 of Pre-Treatment Period and Treatment Periods 1 and 2 (i.e., 3rd epoetin dose of the week) at predose (0 hour) and postdose (0.5, 1, 2, 4, 6, 8, 12, 24 and 48 hours) ] [ Designated as safety issue: No ]

Enrollment: 107
Study Start Date: July 2010
Study Completion Date: January 2011
Primary Completion Date: January 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A: Epoetin Hospira administered IV for three doses Drug: Epoetin Hospira
IV dose 3 times a week.
Active Comparator: Arm B: Epogen administered IV for three doses Drug: Epogen
IV dose 3 times a week

Detailed Description:

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).

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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:

    • Epogen/Epoetin Alfa (Amgen) 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 stores, defined as serum ferritin >= 100 µg/L and transferrin saturation (TSAT) >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).

If hormonal contraceptives are used, the specific contraceptive must have been used for at least 3 months prior to randomization. If the subject is currently using a hormonal contraceptive, she should also use a barrier method during this study and for 1 month after last dose of Study Medication (Dosing Day 3 of Treatment Period 2).

Exclusion Criteria:

  • A subject with any active, uncontrolled systemic disease that in the investigator's opinion may be significant to exclude participation in the study , 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 each 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 III 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 (except flu 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01170078

Locations
United States, California
Downey, California, United States, 90241
Tarzana, California, United States, 91356-6123
United States, Colorado
Denver, Colorado, United States, 80230
United States, Connecticut
Middlebury, Connecticut, United States, 06762
United States, Florida
Lauderdale Lakes, Florida, United States, 33313
Miami, Florida, United States, 33150
Miami, Florida, United States, 33173
United States, Illinois
Gurnee, Illinois, United States, 60031
United States, Kansas
Wichita, Kansas, United States, 67214
United States, Michigan
Detroit, Michigan, United States, 48236
Pontiac, Michigan, United States, 48341
United States, Minnesota
Minneapolis, Minnesota, United States, 55404
United States, Mississippi
Gulfport, Mississippi, United States, 39501
United States, Pennsylvania
Philadelphia, Pennsylvania, United States, 19106
United States, South Carolina
Columbia, South Carolina, United States, 29203
United States, Tennessee
Knoxville, Tennessee, United States, 37923
United States, Texas
Houston, Texas, United States, 77054
Houston, Texas, United States, 77099
San Antonio, Texas, United States, 78229
United States, Virginia
Alexandria, Virginia, United States, 22306
Sponsors and Collaborators
Hospira, Inc.
  More Information

No publications provided

Responsible Party: Hospira, Inc.
ClinicalTrials.gov Identifier: NCT01170078     History of Changes
Other Study ID Numbers: EPOE-10-08
Study First Received: July 23, 2010
Last Updated: June 12, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Hospira, Inc.:
chronic renal failure requiring hemodialysis

Additional relevant MeSH terms:
Kidney Failure, Chronic
Renal Insufficiency
Kidney Diseases
Renal Insufficiency, Chronic
Urologic Diseases
Epoetin alfa
Hematinics
Hematologic Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on August 27, 2015