Anemia and chronic kidney disease stage 5D (patients on stable hemodialysis) MedDRA version: 19.0 Level: PT Classification code 10064848 Term: Chronic kidney disease System Organ Class: 10038359 - Renal and urinary disorders
Conditions
Interventions
Product Name: n/a
Product Code: APO-EPO
Pharmaceutical Form: Solution for injection
INN or Proposed INN: EPOETIN ALFA
CAS Number: 113427-24-0
Current Sponsor code: APO-EPO
Other descriptive name: n/a
Sponsors
APOTEX Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 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
Exclusion criteria
Exclusion criteria: 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the therapeutic equivalence of Apotex's epoetin alfa (APO-EPO) 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) ;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). Co-primary endpoint: Mean Hb concentration during the last 4 weeks of the treatment (evaluation phase). ;Timepoint(s) of evaluation of this end point: Last 4 weeks of the correction phase (evaluation phase): W21, W22, W23 and W24 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary and exploratory efficacy endpoints: •proportion of patients with treatment success, i.e. Hb concentration between 10.0 - 11.0 g/dl for 2 consecutive weeks without any blood transfusion within the preceding 3 months (correction phase); •number of transfusions and proportion of the patients needing blood transfusions during the treatment period (titration, evaluation and maintenance phase); •increase in Hb concentration over time (titration, evaluation and maintenance phase); •change in Hb concentration after initial 4 weeks of treatment; •proportion of patients with maintenance success (maintenance of mean Hb concentration of 10.0-11.0 g/dl for at least 4 consecutive weeks in maintenance phase); •percentage of Hb values outside the target range (11.0 g/dl) (titration, evaluation and maintenance phase); •mean weekly dose of epoetin per kilogram of body weight; •mean Hb concentration during each 4-week-interval; •percentage of hematocrit measurements > 30% (titration, evaluation and maintenance phase); •EPO resistance index (ERI) - mean weekly dose of epoetin per kilogram of body weight divided by mean Hb concentration (titration, evaluation and maintenance phase); •mean iron dose used; •number of low TSAT and ferritin values requiring i.v. supplementation of iron (TSAT<20% and ferritin <100 ng/ml).;Timepoint(s) of evaluation of this end point: Titration phase: W1-W20 Evaluation phase: W21-W24 Maintenance phase: W28 -W48 | — |
Countries
Belarus, Bosnia and Herzegovina, Bulgaria, Czech Republic, Egypt, Georgia, Greece, Hungary, Jordan, Lebanon, Poland, Romania, Serbia, Slovakia, Tunisia, Ukraine
Contacts
Public ContactClinical Trials Info
Accelsiors CRO and Consultancy Services
Outcome results
None listed