Study of safety and efficacy of APO-EPO versus US licensed Procrit® in patients with anemia of chronic kidney disease stage 5D
- Conditions
- MedDRA version: 19.0Level: PTClassification code 10064848Term: Chronic kidney diseaseSystem Organ Class: 10038359 - Renal and urinary disordersAnemia and chronic kidney disease stage 5D (patients on stablehemodialysis)Therapeutic area: Not possible to specify
- Registration Number
- EUCTR2011-005057-31-CZ
- Lead Sponsor
- APOTEX Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 533
1. Written informed consent of the patient;
2. Hb level below 10 g/dl;
3. Age: = 18 years, male or female patients;
4. Patients are on adequate hemodialysis: the minimally adequate dose of hemodialysis given 3 times per week should be an spKt/V (single-pool delivered Kt/V; clearance of urea x dialysis time/volume of distribution) of 1.2 per dialysis based on the Daugirdas method. For treatment periods of less than 5 hours, an alternative minimum dose is a urea reduction rate (URR) of 65%. All types of hemodialysis systems and hemodiafiltration, including high-flux membranes are allowed as long as there is no plan to change the patient’s regimen during the study;
5. Patients suffering from CKD stage 5 and undergoing chronic hemodialysis (three times a week) for a sufficient time so as to become stable (as per inclusion criterion No. 4) for at least 1 month prior to the start of treatment;
6. Sufficient iron stores, defined as serum ferritin = 100 ng/ml and transferrin saturation = 20%. (Patients not meeting these criteria may receive iron supplementation therapy during the Screening and stabilization period to appropriately correct their iron store deficiency to meet the criterion required for randomization);
7. The patients must either be epoetin naïve, or complete a washout period if previously treated with erythropoiesis-stimulating agents (ESA). Patients undergoing wash-out can be randomized if the patient is stable on hemodialysis, with Hb below 10 g/dl and normal iron stores, and has been free of ESA treatment for at least 8 weeks if short-acting ESA were previously used and at least 12 weeks if long-acting ESA (e.g. Pegylated Epoetin) were previously used;
8. Ability to comply with study medication use, study visits, and study
procedures as judged by the investigator;
9. Females of childbearing potential agree to use an acceptable method
of birth control (e.g., abstinence, hormonal or barrier methods, partner sterilization, or IUD) for the duration of the study.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 515
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 18
1.Peritoneal dialysis;
2.CRP = 10 mg/l, as measured with a standard method (if not corrected during the Screening and stabilization period);
3.Uncontrolled hypertension (defined as pre-dialysis diastolic blood pressure = 100 mmHg or systolic blood pressure = 180 mmHg);
4.Primary hematological disorder (e.g. myelodysplastic syndrome, myeloma, sickle cell anemia, hematological malignancy, multiple myeloma hemolytic anemia);
5.Decompensated liver failure;
6.Clinical evidence of concurrent uncontrolled hyperparathyroidism (defined as serum parathyroid hormone (PTH) > 1000 pg/ml);
7.Previous stroke or evident disturbances of brain blood flow, e.g. transient ishemic attack (TIA);
8.Hypothyroidism without adequate replacement therapy (adequate defined as: stable dose of therapy with stable thyroid hormone levels for at least 3 months prior to study entry);
9.Any red blood cell transfusion during the last 3 months (measured at the time of eligibility verification);
10.Heart failure [New York Heart Association (NYHA) class III and IV];
11.Unstable angina pectoris, active cardiac disease and/or cardiac infarction within the last six months;
12.History of or active blood coagulation disease;
13.Thrombocytosis (platelet count > 500,000/µl);
14.Thrombocytopenia (platelet count < 100,000/µl);
15.Leukopenia (white blood cell count < 2,000/µl);
16.History of phenylketonuria;
17.Deficiency in vitamin B12 (if not corrected during the screening and stabilization period);
18.Deficiency in folic acid (if not corrected during the screening and stabilization period);
19.Overt bleeding (acute or chronic bleeding within two months prior to screening);
20.Suspicion of or confirmed occult bleeding (increased reticulocyte count);
21.Clinical evidence of concurrent systemic infection or inflammatory disease;
22.Presence of neutralizing anti-erythropoietin antibodies or suspicion of or known pure red cell aplasia (PRCA);
23.Currently receiving treatment for epilepsy;
24.Major surgery within six months prior to randomization and during the conduct of the trial (except vascular access surgery);
25.Proven HIV, HBV or HCV infection (is to be tested if no test was performed within four weeks prior to the screening);
26.Any androgen therapy within two months prior to screening and during the study;
27.Concomitant immunosuppressive therapy; patients on a short course of steroids (up to 7 days), topical or intranasal steroids are allowed in the study;
28.History of any malignant disease within the last 5 years (except excised non-melanoma skin cancer);
29.Women who are pregnant or breastfeeding;
30.Known history of severe drug-related allergies;
31.Known allergy to one of the ingredients of the test or the reference products or hypersensitivity to mammalian-derived products;
32.Transplant received within 48 weeks prior to the start of the study;
33.Simultaneous participation in another clinical study or having received an Investigational Medicinal Product within three months before randomization in this study.
34.Psychiatric, addictive (drugs or alcohol) or any other disorder that compromises the ability to give an informed consent;
35.Any other condition which at the investigator’s discretion may put the patient at risk or may confound the study results.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To assess the therapeutic equivalence of Apotex's epoetin alfa (APO-EPO)<br>versus US registered epoetin alfa (Procrit®) for correction of the hemoglobin (Hb) concentration in patients with anemia of chronic kidney disease (CKD) stage 5 maintained on stable hemodialysis (CKD stage 5D)<br>;Secondary Objective: To assess the long-term safety and efficacy of APO-EPO in the 6-month maintenance phase of the study.;Primary end point(s): The primary efficacy variable will be the mean weekly dose of epoetin per kilogram of body weight necessary to maintain the Hb level within 10.0-11.0 g/dl during the last 4 weeks of the correction phase (evaluation phase).<br>Co-primary endpoint: Mean Hb concentration during the last 4 weeks of the treatment (evaluation phase).<br>;Timepoint(s) of evaluation of this end point: Last 4 weeks of the correction phase (evaluation phase): W21, W22, W23 and W24
- Secondary Outcome Measures
Name Time Method