Treatment of anemia due to chronic kidney disease in patients not yet on hemodialysis MedDRA version: 14.1 Level: LLT Classification code 10064848 Term: Chronic kidney disease System Organ Class: 100000004857
Conditions
Interventions
Product Name: APO-EPO
Product Code: n/a
Pharmaceutical Form: Solution for injection
INN or Proposed INN: EPOETIN ALFA
CAS Number: 113427-24-0
Current Sponsor code: n/a
Other descriptive name: Erythrop
Sponsors
APOTEX Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Written informed consent of the patient; 2. Hb level =65 years) yes F.1.3.1 Number of subjects for this age range 16
Exclusion criteria
Exclusion criteria: 1. Patients on regular hemodialysis or peritoneal dialysis; 2. C-Reactive protein (CRP) > 10 mg/l, as measured with a standard method; 3. Uncontrolled hypertension (defined as diastolic blood pressure = 100 mmHg or systolic blood pressure = 180 mmHg); 4. Primary hematological disorder (e.g. myelodysplastic syndrome, multiple myeloma, sickle cell anemia, hematological malignancy, 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 ischemic attack (TIA); 8. Hypothyroidism without adequate replacement therapy (adequate defined as stable dose with stable thyroid hormone levels for at least 3 months prior to Screening); 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, stroke and/or myocardial infarction within the last six months prior to screening; 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 6-week-anemia-work-up period); 18. Deficiency in folic acid (if not corrected during the 6-week-anemia- work-up period); 19. Overt bleeding (acute or chronic bleeding within the last 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 antibodies or suspicion of or known pure red cell aplasia (PRCA); 23. Currently receiving treatment for epilepsy; 24. Major surgery within the last six months prior to Screening and during the conduct of the trial; 25. Proven HIV, HBV or HCV infection (to be tested if no test was performed within four weeks prior to the screening); 26. Any androgen therapy within the last two months prior to screening and during the study; 27. Concomitant immunosuppressive therapy; patients on a short course of steroids (e.g. treatment of a gout attack), topical or intranasal steroids are allowed in the study; 28. History of malignant disease within the last 5 years prior to Screening; 29. Pregnant or breastfeeding women; 30. Known history of severe drug-related allergies; 31. Known allergy to one of the ingredients of the test or reference product (including the preservative used for the multi-dose IP) or Venofer or hypersensitivity to mammalian-derived products; 32. Transplant received within 48 weeks prior to study entry; 33. Simultaneous participation in another clinical study or participation in a study within 3 months before randomization; 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 opinion may put the patient at risk or may confound the study results.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the safety and efficacy of APO-EPO as compared to the reference product, Epogen®/Procrit® for correction of hemoglobin (Hb) concentrations in patients with anemia and chronic kidney disease (CKD) not yet on dialysis.;Secondary Objective: ? To assess the long-term safety and efficacy of APO-EPO in the 6-month safety extension period (maintenance phase) of the study. ? To evaluate the bioequivalence of APO-EPO and Epogen®/Procrit® in a pharmacokinetic (PK)/pharmacodynamic (PD) substudy.;Primary end point(s): The primary efficacy variable will be the proportion of patients achieving a hemoglobin response during the 24-week correction phase, defined as an increase in hemoglobin of =1.0 g/dl from baseline and a hemoglobin concentration 10-11 g/dl. The co-primary, pharmacodynamic endpoint for bioequivalence evaulation will be the area under the effect curve (AUEC) of Hb, at four weeks of treatment (multiple dose administration) in the correction phase. The co-primary, pharmacokinetic endpoints for bioequivalence evaluation will be the area under the curve (AUC48, md) and the maximum concentration (Cmax) of epoetin at four weeks of treatment (multiple dose administration) in the correction phase and pharmacokinetic parameters after single dose administration on Day 1 of the correction phase: Cmax,sd and AUC of epoetin (AUC0–48, sd).;Timepoint(s) of evaluation of this end point: Every second week of the correction phase | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Clinical endpoints: ? Proportion of patients with treatment success, i.e. Hb concentration 10-11 g/dl for 2 consecutive weeks without any blood transfusion within the preceding 3 months (correction phase) - Number of transfusions and proportion of patients needing blood transfusions during the treatment period (correction and maintenance phase); - Increase in Hb concentration during the treatment period (correction and maintenance phase); - Change in Hb concentration after the initial 4 weeks of treatment; - Proportion of patients with maintenance success (maintenance of mean Hb concentration of 10-11 g/dl for at least 4 consecutive weeks in the maintenance phase); - Percentage of Hb values outside the target range (>11 g/dl) (correction 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% (correction and maintenance phase). PK/PD endpoints: ? Pharmacokinetic parameters after single dose administration on Day 1 of the correction phase: baseline corrected AUC0–48, sd; baseline corrected Cmax, sd; tmax, sd; t½, sd; PTF; and Cmin; ? Pharmacokinetic parameters at four weeks of treatment (multiple dose administration) in the correction phase: baseline corrected AUC0–48, md; baseline corrected Cmax, md; tmax, md; t½ md; PTF; and Cmin; ? Pharmacodynamic parameters at four weeks of treatment (multiple dose administration) in the correction phase: AUEC of Hb after single dose administration; Cmax of RBC; Cmax of Hb; HCT; and Ret%. Safety endpoints: ? Occurrence of anti-erythropoietin antibodies; ? Proportion of patients with an increase in Hb concentration of > 1.0 g/dl for 4 weeks; ? Number of Hb increases =2 g/dl within any 4-week period - both the number of study subjects and the number of episodes of such an increase; ? Maximum Hb increase within any 4-week period; ? Ratings of tolerability and evaluat | — |
Countries
Bosnia and Herzegovina, Bulgaria, Czech Republic, Hungary, Poland, Romania, Russian Federation, Serbia, Slovakia, Ukraine
Contacts
Public ContactClinical Trials Info
Accelsiors CRO and Consultancy Services
Outcome results
None listed