Erythropoietin is a glycoprotein which stimulates red blood cell production. It is produced in the kidney and stimulates the division and differentiation of committed erythroid progenitors in the bone marrow. Erythropoietin, a 165 amino acid glycoprotein manufactured by recombinant DNA technology, has the same biological effects as endogenous erythropoietin. Erythropoietin binds to the surface receptor of erythroid precursor cells and activates signal transduction pathways that interfere with apoptosis and stimulates erythroid cell proliferation. Recombinant human erythropoietin is a substitute for the deficiency observed in CKD, therapy of anemia often involves many other issues such as Anemia in patients with non-myeloid malignancies where anemia is due to the effect of concomitantly administered chemotherapy, Anemic patients (hemoglobin \> 10 to \< 13 g/dL) scheduled to undergo elective, noncardiac, nonvascular surgery to reduce the need for allogeneic blood transfusions, Anemia related to therapy with zidovudine in HIV-infected patients are also needed to be considered in order to effectively correct anemia, reduce costs and minimize side effects.
• Age ≥ 18 years.
BMI of 18.0-30.0kg/m2.
Voluntarily participants who agree to observe the precautions in writing after receiving a complete explanation of this trial.
Willingness and ability to undertake all scheduled visits and assessments.
• Subjects with any previous exposure to erythropoiesis stimulating agents.
History of clinically significant illness related to liver (including viral hepatitis), kidney, nervous system, immune system, respiratory system, endocrine system, cardiovascular system, blood system and tumor as well as mental illness (mood disorder, obsessive-compulsive disorder, etc.)
Hypersensitivity or clinically significant hypersensitivity to the drug (e.g. aspirin, antibiotics, etc.)
Those whose results meet more than one of the followings in the screening including re-test; Hemoglobin level below 12g/dL or over 17g/dL, Ferritin level below 21.8ng/mL, Transferrin level below 190mg/dL, Reticulocyte level >2.5%, erythrocytes level > 5.2x 106/mm3, platelets or serum potassium level over normal range.
Crossover
Erythropoietin alfa
Biological/VaccineErythropoietin 4000 IU Injection, for subcutaneous injection.
Peak Plasma Concentration (Cmax)
The PK parameter Cmax shall be calculated by noncompartmental analysis using Phoenix® WinNonlin. The maximum observed serum EPO concentration (Cmax) shall be directly obtained from the data.
Reticulocyte count (%)
As primary PD parameter, maximum effect change (Delta Emax) and the area under the baseline-adjusted effect curve (Delta AUEC) shall be calculated by the linear trapezoidal method for the RET count.
Area under the plasma concentration versus time curve (AUC)
The PK parameters shall be calculated by noncompartmental analysis using Phoenix® WinNonlin. The maximum observed serum EPO concentration (Cmax) and the time of Cmax (Tmax) shall be directly obtained from the data. The AUClast shall be calculated by the linear trapezoidal method up to Tmax and by the log trapezoidal method after Tmax. The area under the curve extrapolated to infinity (AUCinf) shall be obtained with the following formula: AUCinf=AUClast+Clast, where Clast is the last observed serum EPO concentration and lambda z is a calculated terminal elimination rate constant.
t1/2
The terminal half-life (t1/2) shall be calculated by dividing natural-log2 by lambda z.
Immunogenicity
By measuring Anti-drug Antibody (ADA) formation.
Hemoglobin
Mean absolute change in Hb levels between the baseline period (pre dose) and the evaluation period.
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Incepta Pharmaceuticals Ltd
Lead sponsor
Institute for Developing Science and Health Initiatives, Bangladesh
Collaborator
