Multicenter open-label randomized crossover bioequivalence study of Flugarda® tablets (CJSC BIOCAD, Russia) and Fludara® tablets (Genzyme Europe B.V., the Netherlands) in patients with B-cell chronic lymphocytic leukemia.
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 18
- 试验地点
- 8
- 主要终点
- The assessment of the investigational products’ bioequivalence will be performed by comparing the following PK parameters: the maximal plasma concentration of 2-fluoro-ara-Р(the main fludarabine metabolite) Cmax, area under concentration-time curve (AUC) from the moment of drug administration till 24 hours and till infinity (AUC (0-24) and AUC(0-∞), respectively) after a single oral administration of the test drug and the reference drug.
研究概览
简要总结
It is multicenter open-label randomized crossoverbioequivalence study of Flugarda® tablets (CJSC BIOCAD, Russia) and Fludara® tablets (Genzyme Europe B.V., theNetherlands) in patients with B-cell chronic lymphocytic leukemia.18patients with B-cell CLL will be recruited into the study. After informed consent form signing and screeningexamination, subjects will be randomly assigned into one of two groups (#1 or #2) in a 1:1 ratio.The study will be conducted at 6 sites of India.
Fludarabineis an effective drug that is well tolerated by patients suffering from lymphoproliferativediseases. Fludarabine is a cytostatic agent with no significant negative impacton the quality of patients’ life.The main objective of the study is to compare the concentration of the main fludarabinemetabolite (2-fluoro-arabinofuranosyladenine – 2- fluoro-ara-Ð) within 24 hours after a single oral administration of Flugarda® at a dose of 40 mg/m2 under fasting conditionor Fludara® at the same dosein patients with B-cell CLL. and to evaluate the rate and severity of adverseevents after oral administration of Flugarda® at a dose of 40 mg/m2 and Fludara® at the same dose for 5 straight days.
研究设计
- 研究类型
- Interventional
- 分配方式
- Computer generated randomization
- 盲法
- Open Label
入排标准
- 年龄范围
- 18.00 Year(s) 至 75.00 Year(s)（—）
- 性别
- All
入选标准
- •1.Signed informed consent form.
- •2.Patients with documented stage A or B of B-cell CLL according to Binet classification requiring treatment.
- •3.18-75 years of age inclusive.
- •5.Life expectancy greater than 6 months from the date of study enrollment.
- •Pre-specified laboratory values: hemoglobin ≥ 100 g/L, white blood cells (WBC) ≥ 2.5 Ñ… 109/L, absolute neutrophil count ≥ 1.5 Ñ… 109/L, platelet count ≥ 100 Ñ… 109/L, liver enzymes (AST, ALT, ALP, GGT) ≤ 2.5 x upper limit of normal (ULN), total bilirubin ≤ 2.0 mg/dL, creatinine level ≤ ULN.
- •7.Negative test results for hepatitis B, C, HIV, and syphilis dated no more than 4 weeks before the screening examination.
- •8.Body Mass Index (BMI) within the normal range (18.5-24.99 kg/m2).
- •9.Hemodynamic parameters within normal range: systolic blood pressure (SBP) within 100-130 mm Hg, diastolic blood pressure (DBP) within 60-90 mm Hg, heart rate within 50-90 beats per minute.
- •10.Body temperature ≤ 38°С for a week before the study inclusion.
- •11.Patient’s ability to comply with the requirements of the Protocol (according to an Investigator’s opinion).
- •12.Male and female subjects with normal reproductive function and their sexual partners are aware and willing to use voluntarily reliable methods of contraception starting from 1 week prior to study entry and 4 weeks after administration of the last dose of the test drug.
- •This requirement does not apply to patients who had operative sterilization or those defined as post-menopausal (documented) within last 2 years.
- •Reliable methods of contraception suggest using 1 barrier method in combination with 1 of the following methods: spermicides, intra-uterine device.
- •13.Willingness not to drink alcohol within 24 hours prior to the first dosing of the test drug/the reference drug and within 48 hours after the last dosing.
- •14.Willingness not to drink grapefruit juice or grapefruit-containing foods within 72 hours prior to the first dosing of test drug/reference drug and within 72 hours after the last dosing in each study period.
排除标准
- •1.Aggravated allergological anamnesis (e.g., history of multi-drug allergy, anaphylactic shock, etc). 2.Known hypersensitivity or idiosyncratic reaction to fludarabine or any other ingredients of the test drug or the reference drug. 3.Confirmed lactose intolerance or other rare hereditary diseases such as saccharose and fructose intolerance, lactase and sucrase-isomaltase deficiency or glucose-galactose malabsorption. 4.Psychiatric disorders and other conditions that might interfere with ability of a patient to follow the study Protocol. 5.History of gastrointestinal surgery (with the exception of appendectomy performed no later than 30 days prior to the screening examination). Other surgeries should be performed not later than 30 days prior to the screening examination. 6.Any acute or chronic infection at the moment of screening examination; acute bacterial, viral, or mycotic infection (for example, cystitis) less than 4 weeks prior to the screening examination. 7.Urinary retention in the past medical history or at screening examination. 8.Inability to insert the venous catheter for blood sampling (e.g., due to a skin disease at the venipuncture sites). 9.Any diseases or other conditions that might affect the pharmacokinetics of the test drug/the reference drug, for example:.
- •intestinal malabsorption;.
- •severe hepatic or renal dysfunction (liver enzymes level (AST, ALT, ALP, GGT) > 2.5 x ULN, total blood bilirubin level > 2.0 mg/dL, plasma creatinine level > ULN);.
- •cardiovascular disorders (severe refractory idiopathic hypertension, decompensated cardiac disorders (III-IV class of chronic heart failure according to NYHA);.
- •decompensated respiratory insufficiency, tumor infiltration of lungs;.
- •neuroendocrine disorders (e.g., severe refractory diabetes mellitus);.
- •autoimmune disorders; 10.A history of any other neoplasm with the exception of adequately treated basal-cell carcinoma or cervical carcinoma in situ and cases with the remission period not less than 5 years. 11.Bone marrow radiation exposure (> 30%) in a history. 12.The use of the medicines including non-prescription and dietary supplements, which have pronounced influence on hemodynamics, liver function etc. (barbiturates, omeprazole, cimetidine etc.), less than 30 days prior to the study initiation; received blood less than 2 weeks prior to the screening examination. 13.Conditions requiring the constant use of systemic corticosteroids. 14.Pregnancy and lactation. 15.Smoking more than 10 cigarettes per day. 16.Consumption of more than 10 units of alcohol per week (1 unit is equivalent to 0.5 L of beer, 200 mL of wine or 50 mL of pure alcohol) or a history of alcoholism, narcomania or drug abusing. 17.Donation of ≥ 450 mL of blood or plasma within 3 months prior to the study enrollment. 18.Participation in any clinical trials less than 3 months prior to the study enrollment. 19.Simultaneous participation in other clinical trials. 20.Previous participation in this study.
结局指标
主要结局
The assessment of the investigational products’ bioequivalence will be performed by comparing the following PK parameters: the maximal plasma concentration of 2-fluoro-ara-Р(the main fludarabine metabolite) Cmax, area under concentration-time curve (AUC) from the moment of drug administration till 24 hours and till infinity (AUC (0-24) and AUC(0-∞), respectively) after a single oral administration of the test drug and the reference drug.
时间窗: 0 min, 15 mins, 30 mins, 45 mins,50 mins, 1hr, 1hr 30 mins, 2 hrs, 3 hrs, 4 hrs,6 hrs, 8 hrs, 10 hrs and 24 hrs after administration of the test or reference drug.
次要结局
- •AEs and SAEs incidence;(•Grade 3-4 AEs incidence according to CTCAE 4.03;)