Randomized, Double-blinded, Two-treatment, Two-periods, Single-dose, Crossover, PK, PD, Safety, and Immunogenicity Study of Erythropoietin of Incepta Pharmaceuticals Ltd With Eprex of Janssen-Cilag Ltd in Healthy Adult Subjects
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 56
- 试验地点
- 1
- 主要终点
- Peak Plasma Concentration (Cmax)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •• Age ≥ 18 years.
- •BMI of 18.0-30.0kg/m
- •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.
- •Subject who have no evidence of underlying disease during screening, medical history and whose physical examination is performed within 28 days prior to commencement of the study.
- •Subjects whose screening laboratory values are within normal limits or considered by the Investigator to be of no clinical significance.
- •Non-smokers, ex-smokers and light smokers can be included in the study. "Light smokers are defined as someone smoking < 10 cigarettes per day, ex-smokers as someone who completely stopped smoking for at least 03 months.
- •No alcohol dependence, alcohol abuse or drug abuse (Amphetamines, Cocaine, Tetra Hydro Cannabinoids, Benzodiazepines, Barbiturates and Opioids) within the past one year.
- •Subjects should not have consumed grape fruit juice or its products 72 hours before dosing and throughout the study periods.
- •For Female Subjects:
- •Subjects having negative urine pregnancy test.
- •Female of child bearing potential practicing an acceptable method of birth control for the duration of the study as judged by the Investigator(s), such as condoms, foams, jellies, diaphragm, intrauterine device (IUD), or abstinence.
- •Postmenopausal for more than 1 year.
- •Surgically sterile (bilateral tubal ligation, bilateral oophorectomy, or hysterectomy has been performed on the subject).
排除标准
- •• 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.
- •Positive on the HIV antibody, HBsAg, HCV (Hepatitis C Virus) antibody tests.
- •Those whose vital signs measured in sitting position after resting over 3 minutes meet more than one of the following; Systolic BP below 90mmHg or over 160mmHg, Diastolic BP below 50mmHg or over 100mmHg, Pulse rate over
- •Those who received the following diagnosis within 6 months prior to the screening; Hemoglobinopathy (e.g., homozygous sickle-cell disease, thalassemia of all kinds), Chronic or uncontrollable inflammatory diseases (e.g., rheumatoid arthritis, systemic erythematosus)
- •Those who participated other clinical trials and was administered other drugs within 3 months prior to the scheduled dose.
- •Those who bled over 400mL or donated blood within 8 weeks prior to the scheduled first dose.
- •Those who are considered inappropriate for the trial by the trial investigator based on the result of clinical laboratory test or due to other reasons.
- •Employees of Investigational sites, individuals directly involved with the conduct of the study or immediate family members thereof, prisoners, and persons who are legally institutionalized.
研究组 & 干预措施
Erythropoietin 4000 IU Injection of Incepta Pharmaceuticals Ltd
Erythropoietin 4000 IU Injection, subcutaneous injection manufactured by Incepta Pharmaceuticals Ltd will be administered.
干预措施: Erythropoietin alfa (Biological)
Eprex 4000 by Janssen-Cilag Ltd
Eprex 4000, subcutaneous injection manufactured by Janssen-Cilag Ltd will be administered.
干预措施: Erythropoietin alfa (Biological)
结局指标
主要结局
Peak Plasma Concentration (Cmax)
时间窗: 144.00±1* hours following drug administration after each dose.
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 (%)
时间窗: 312±1 hours post dose.
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)
时间窗: 144.00±1* hours following drug administration
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.
次要结局
- t1/2(144.00±1* hours following drug administration.)
- Immunogenicity(At 00.00 hours of period I and at 312±1 hours post dose of period II)
- Hemoglobin(From baseline and up to 312±1 hours following drug administration)