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.
In this study, 56 healthy adult volunteers will participate in a randomized, double-blinded, balanced, two-treatment, two-period, two-sequence, single-dose crossover trial. Each subject will receive a single subcutaneous injection of either Erythropoietin 4000 IU manufactured by Incepta Pharmaceuticals Ltd (test product) or Eprex 4000 IU manufactured by Janssen-Cilag Ltd (reference product) under fasting conditions, with a 28-day washout period between doses. The primary aim of the study is to compare the pharmacokinetic and pharmacodynamic profiles of the two products. Additionally, the study will assess immunogenicity by measuring serum anti-drug antibodies (ADA) and evaluate the safety of both formulations throughout the study duration.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
56
Erythropoietin 4000 IU Injection, for subcutaneous injection.
Universal Medical College and Hospital
Dhaka, Dhaka Division, Bangladesh
RECRUITINGPeak 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.
Time frame: 144.00±1* hours following drug administration after each dose.
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.
Time frame: 312±1 hours post dose.
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.
Time frame: 144.00±1* hours following drug administration
t1/2
The terminal half-life (t1/2) shall be calculated by dividing natural-log2 by lambda z.
Time frame: 144.00±1* hours following drug administration.
Immunogenicity
By measuring Anti-drug Antibody (ADA) formation.
Time frame: At 00.00 hours of period I and at 312±1 hours post dose of period II
Hemoglobin
Mean absolute change in Hb levels between the baseline period (pre dose) and the evaluation period.
Time frame: From baseline and up to 312±1 hours following drug administration
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