A Randomized, Two-treatment, Two-period, Crossover, Single-dose, Subcutaneous Injection Study Comparing the Pharmacokinetics, Pharmacodynamics, and Safety of Nanokine Manufactured by Nanogen Pharmaceutical Biotechnology Joint Stock Company With Eprex 4000 U Manufactured by Cilag AG in Healthy Volunteers
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 44
- 主要终点
- AUC0-inf
研究概览
简要总结
This clinical trial aims to compare the pharmacokinetic (PK), pharmacodynamic (PD) parameters, and safety between Nanokine of Nanogen Pharmaceutical Joint Stock Company and Eprex® of Janssen Cilag Ltd on healthy male volunteers.
The biosimilarity of erythropoietin (EPO) between Nanokine (test) and Eprex® (comparator) was evaluated in a randomized, two-treatment, two-period, crossover, single-dose study.
Subjects received a 4,000 IU subcutaneous dose of either formulation, followed by the alternate after a 28-day washout.
Key pharmacokinetic (PK) parameters, Cmax and AUCinf, were assessed, with geometric mean ratios/GMR (90% CI) falling within the regulatory range (0.80-1.25). Pharmacodynamic (PD) marker (reticulocyte count) need to show comparable effects.
Safety evaluation (adverse events and serious adverse events, other safety assessments such as vital signs, testing, and examination) supports their interchangeability in clinical use.
详细描述
Erythropoietin (EPO) is a glycoprotein hormone essential for red blood cell (RBC) formation, primarily produced in the kidneys. Recombinant human erythropoietin (rHuEPO) or erythropoiesis-stimulating agents (ESAs) are used to treat anemia in chronic renal failure, chemotherapy-induced anemia, and to reduce transfusion needs in surgery.
Nanokine, currently considered as a follow-on biological product of Eprex® developed by Nanogen Biopharmaceutical JSC, is produced in CHO cells. This study evaluates the bioequivalence of Nanokine and Eprex® in healthy volunteers, comparing pharmacokinetics (PK), pharmacodynamics (PD), and safety.
A randomized, open-label, single-dose, two-sequence crossover trial is conducted in 44 healthy male volunteers (aged 19-45 years, BMI 18.0-28.0 kg/m²). Participants received a 4,000 IU subcutaneous injection of either Eprex® or Nanokine, followed by the alternate after a 28-day washout. Blood samples for PK analysis were taken at multiple time points up to 144 hours postdose, while PD markers (reticulocytes) were measured up to 312 hours postdose.
The purpose of this clinical study is to evaluate and compare the pharmacokinetics, pharmacodynamics, and safety profile of NANOKINE (manufactured by Nanogen Pharmaceutical Biotechnology Joint Stock Company) with Eprex 4000 U (manufactured by Cilag AG).
This is a randomized, two-treatment, two-period, crossover study involving a single-dose subcutaneous injection administered to healthy volunteers.
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
- None (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Male, aged 18 to 45 years.
- •Body weight 50 kg - 70 kg, BMI 18 - 28 kg/m², calculated per Metropolitan Index 1983 for adults.
- •At the time of screening, the subject is determined to be healthy by the investigator through a general clinical examination.
- •Laboratory test results for ECG, hematology and biochemistry (fasting glucose, urea, AST, ALT, creatinine) are within normal limits or assessed by the investigator as normal/eligible for study participation.
- •Screening test results:
- •Hemoglobin 125-175 g/L;
- •Vitamin B12 200-300 pg/mL;
- •Ferritin 22-400 ng/mL;
- •Transferrin 200-360 mg/dL;
- •Albumin 35-52 g/L;
- •Reticulocytes, red blood cells, and platelets within normal range;
- •Negative urine drug screen;
- •Negative HBsAg, anti-HCV and HIV.
- •Voluntarily participates in the study and has signed the informed consent form.
排除标准
- •Lacks civil act capacity.
- •History of severe allergic reaction or anaphylaxis to biological products.
- •Use of Erythropoiesis Stimulating Agents (ESAs) or immunoglobulins within 3 months prior to screening.
- •History of seizures, epilepsy, or current disorders of the cardiovascular, respiratory, hepatic, renal, gastrointestinal, immune, hematologic, endocrine, nervous system, or psychiatric illness (as determined by the examining physician).
- •Recent illness within 2 weeks prior to screening (based on medical history and clinical examination).
- •History of blood loss >450 mL or blood donation within 28 days prior to the first scheduled dose.
- •History of illicit drug use.
- •Recent history of alcohol abuse (defined as regular alcohol consumption within 6 months prior to screening, with average weekly intake >21 units/week. One unit equals 8 g ethanol, equivalent to: 240 mL (half a glass) of beer, or 100 mL (1 glass) of wine, or 25 mL (1 shot) of spirits).
- •Recent history of tobacco abuse (defined as smoking on average >10 cigarettes/day within 3 months prior to screening, or inability to abstain from smoking throughout the study period).
- •Excessive caffeine consumption (more than 5 cups of coffee per day).
- •Special dietary habits or inability to consume meals provided by the study site.
- •Currently participating in another clinical study, or has participated in a clinical study with another investigational product within the last 3 months.
- •Planning to conceive during the study period or unwilling to use contraception throughout the study.
研究组 & 干预措施
Nanokine 4000 IU
Nanokine 4000 IU, prefilled syringe, subcutaneous injection. Nanokine 4000 IU will be transported and handed over to the Study Center by the Sponsor. Nanokine 4000 IU should be stored in a refrigerator of 2-8°C.
干预措施: Erythropoietin alfa (Biological)
Eprex 4000 IU
Eprex 4000 IU, pre-closed syringe, subcutaneous injection. Eprex 4000 IU will be transported and handed over directly to the Study Center by the supplier (with a contract with the Sponsor).
Eprex 4000 IU should be stored in a refrigerator of 2- 8 °C.
干预措施: Erythropoietin alfa (Biological)
结局指标
主要结局
AUC0-inf
时间窗: 10 minutes before administration (day 1/day 29); 1, 2, 4, 6, 8, 10, 12, 14,16, 24, 36, 48, 72, 96, 120, 144 hrs after administration for each period]
Area under the plasma concentration versus time curve from time 0 to infinity
Cmax
时间窗: 10 minutes before administration (day 1/day 29); 1, 2, 4, 6, 8, 10, 12, 14,16, 24, 36, 48, 72, 96, 120, 144 hrs after administration for each period]
Peak plasma concentration
AUC0-t
时间窗: Pre-dose (30, 20, and 10 minutes before administration) and post-dose (30 minutes, 3, 6, 9, 12, 14, 15, 24, 30, 48, 72, 96, 120, and 144 hours after administration)
Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Quantifiable Concentration (AUC0-t)
Cmax
时间窗: Pre-dose (30, 20, and 10 minutes before injection) and post-dose (30 minutes, 3, 6, 9, 12, 14, 15, 24, 30, 48, 72, 96, 120, and 144 hours after injection).
Peak plasma concentration
AUC0-t of RET
时间窗: Pre-dose (10 minutes before administration) and post-dose (12, 24, 48, 72, 96, 120, 144, 168, 216, and 312 hours after administration)
Area Under the Effect-Time Curve of Reticulocyte Count (AUC0-t of RET)
Cmax of RET
时间窗: Pre-dose (10 minutes before administration) and post-dose (12, 24, 48, 72, 96, 120, 144, 168, 216, and 312 hours after administration)
Maximum Observed Effect of Reticulocyte Count (Cmax of RET)
次要结局
- AUClast(10 minutes before administration (day 1/day 29); 12, 24, 48, 72, 96, 120, 144, 216, 312 hrs after administration for each period])
- Clast.obs(10 minutes before administration (day 1/day 29); 12, 24, 48, 72, 96, 120, 144, 216, 312 hrs after administration for each period])
- Tmax(10 minutes before administration (day 1/day 29); 12, 24, 48, 72, 96, 120, 144, 216, 312 hrs after administration for each period])
- T1/2(10 minutes before administration (day 1/day 29); 12, 24, 48, 72, 96, 120, 144, 216, 312 hrs after administration for each period])
- Tlast(10 minutes before administration (day 1/day 29); 12, 24, 48, 72, 96, 120, 144, 216, 312 hrs after administration for each period])
- CL.obs(10 minutes before administration (day 1/day 29); 12, 24, 48, 72, 96, 120, 144, 216, 312 hrs after administration for each period])
- Vz.obs(10 minutes before administration (day 1/day 29); 12, 24, 48, 72, 96, 120, 144, 216, 312 hrs after administration for each period])
- Lambda.z(10 minutes before administration (day 1/day 29); 12, 24, 48, 72, 96, 120, 144, 216, 312 hrs after administration for each period])
- TEmax(10 minutes before administration (day 1/day 29); 12, 24, 48, 72, 96, 120, 144, 216, 312 hrs after administration for each period])
- Adverse events(Baseline to 312 hours after the crossover dose)
- ΔEmax(10 minutes before administration (day 1/day 29); 12, 24, 48, 72, 96, 120, 144, 216, 312 hrs after administration for each period])
- ΔAUEC0-inf(10 minutes before administration (day 1/day 29); 12, 24, 48, 72, 96, 120, 144, 216, 312 hrs after administration for each period])
- Hemoglobin(10 minutes before administration (day 1/day 29); 12, 24, 48, 72, 96, 120, 144, 216, 312 hrs after administration for each period])
- Hematocrit(10 minutes before administration (day 1/day 29); 12, 24, 48, 72, 96, 120, 144, 216, 312 hrs after administration for each period])
- RBC count(10 minutes before administration (day 1/day 29); 12, 24, 48, 72, 96, 120, 144, 216, 312 hrs after administration for each period])
- AUC0-inf(Pre-dose (30, 20, and 10 minutes before administration) and post-dose (30 minutes, 3, 6, 9, 12, 14, 15, 24, 30, 48, 72, 96, 120, and 144 hours after administration))
- Tmax(Pre-dose (30, 20, and 10 minutes before administration) and post-dose (30 minutes, 3, 6, 9, 12, 14, 15, 24, 30, 48, 72, 96, 120, and 144 hours after administration))
- T1/2(Pre-dose (30, 20, and 10 minutes before administration) and post-dose (30 minutes, 3, 6, 9, 12, 14, 15, 24, 30, 48, 72, 96, 120, and 144 hours after administration))
- CL.obs(Pre-dose (30, 20, and 10 minutes before administration) and post-dose (30 minutes, 3, 6, 9, 12, 14, 15, 24, 30, 48, 72, 96, 120, and 144 hours after administration))
- Vz.obs(Pre-dose (30, 20, and 10 minutes before administration) and post-dose (30 minutes, 3, 6, 9, 12, 14, 15, 24, 30, 48, 72, 96, 120, and 144 hours after administration).)
- Lambda.z(Pre-dose (30, 20, and 10 minutes before administration) and post-dose (30 minutes, 3, 6, 9, 12, 14, 15, 24, 30, 48, 72, 96, 120, and 144 hours after administration))
- RBC Count(Pre-dose (10 minutes before administration) and post-dose (12, 24, 48, 72, 96, 120, 144, 168, 216, and 312 hours after administration))
- Hb(Pre-dose (10 minutes before administration) and post-dose (12, 24, 48, 72, 96, 120, 144, 168, 216, and 312 hours after administration))