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
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 107
- 主要终点
- Baseline-adjusted area under the serum epoetin concentration curve from the time of dose administration to 48 hours (AUC0-48)
研究概览
简要总结
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.
详细描述
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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).
排除标准
- •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 B
- •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.
研究组 & 干预措施
Arm A: Epoetin Hospira administered IV for three doses
干预措施: Epoetin Hospira (Drug)
Arm B: Epogen administered IV for three doses
干预措施: Epogen (Drug)
结局指标
主要结局
Baseline-adjusted area under the serum epoetin concentration curve from the time of dose administration to 48 hours (AUC0-48)
时间窗: 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)
Maximum serum epoetin concentration (Cmax)
时间窗: 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)
AUC from time of dose administration to the time of the last measurable concentration (AUC0-t)
时间窗: 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)
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.
次要结局
- Elimination rate Constant (λz)(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))
- Volume of Distribution (Vd)(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))
- Dose-adjusted Cmax(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))
- Elimination halflife (t1/2)(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))
- AUC from time of dose administration to the time of the last measurable concentration (AUC0-t)(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))
- Clearance (CL)(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))