An Open-label, Randomized, Three-period, Two-treatment, Three-sequence, Reference replicated, Crossover, Multicentre, Single-dose Bioequivalence Study of Capecitabine Tablets 500 mg of Cadila Healthcare Ltd., India and ‘XELODA®’ (Capecitabine) Tablets 500 mg of Genentech USA Inc., USA in Metastatic Breast Cancer, Duke’s C Colon Cancer or Metastatic Colorectal Cancer Patients under Fed Conditions
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 54
- 试验地点
- 9
- 主要终点
- To characterize the pharmacokinetic profile of the sponsor’s test formulation (Capecitabine Tablets 500 mg, Manufactured by Cadila Heathcare Limited, India) relative to that of reference formulation (XELODA® 500 mg tablets, Manufactured by Genentech USA Inc. USA) in patients of Metastatic Breast Cancer, Duke’s C Colon Cancer or Metastatic Colorectal Cancer under fed condition and to assess the bioequivalence.
研究概览
简要总结
This study is a multi-center, open-label, single-dose, three-period, randomized, two-treatment, crossover study to investigate the bioequivalence of a single formulation of Cadila Healthcar’s Capecitabine Tablets, 500 mg compared to the Genentech’s Xeloda® Tablets, 500 mg. xml:namespace prefix = o ns = "urn:schemas-microsoft-com:office:office" /
The single-dose pharmacokinetics of capecitabine will be characterized in fifty-four (54) adult, male and not of childbearing potential female volunteers with metastatic breast cancer, Duke’s C colon cancer after complete resection, or metastatic colorectal cancer for whom the drug is indicated either alone or in combination with another drug.
Each patient will receive a capecitabine dose of 1250 mg/m2 dose in the morning under fed conditions. The dose will be comprised of multiples of the 500 mg tablet. In order to determine the pharmacokinetic parameter (CPEAK and AUC) intra-patient variability for Xeloda®, each patient will receive Xeloda® twice during the course of the study.
Subjects will be housed at least 11 hours prior to the first dose of investigational product until at least 10 hours after the final dose of investigational product. Blood samples (1×4 mL except predose 8 mL) will be collected in K2 EDTA tubes 30 minutes prior to drug dosing and 0.25, 0.50, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8 and 10 hours post-dose. Patients will receive their regularly scheduled dose of capecitabine 12 hours after the morning dose of investigational product. Patients will receive a single dose of the test product and two doses of the reference product between Cycle Day 2 and Cycle Day 13 (inclusive) of a single treatment cycle.
In between investigational (test/reference) product administration, the patient will continue to receive their standard dosing regimen medication.
The collected blood samples will be cooled in an ice bath or sample cooling rack (e.g. Kryorack) and centrifuged under refrigeration as soon as possible.
Plasma will be extracted, divided into two (2) equal aliquots, and stored in suitably labeled tubes at −20°C ± 10°C or colder until shipment to the central storage site. Samples will be stored in freezer at -70oC+ 20oC at analytical site until analyzed. For each subject the duration of the study will be 3 to 11 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 79.00 Year(s)（—）
- 性别
- All
入选标准
- •Patients must be receiving stable doses of Capecitabine (e.g.: 2500 mg/m2/day in two divided doses of 1250 mg/m2 , for 2 weeks followed by a 1 week rest period given as 3 week cycles) for the treatment of metastatic breast cancer, Duke’s C colon cancer following complete resection, and metastatic colorectal carcinoma.
- •Patients must have completed at least one cycle.
- •Males or non pregnant or non lactating females of age ≥ 18 years and ≤ 79 years.
- •a)Females of childbearing potential must have a negative serum beta human chorionic gonadotropin (β-HCG) pregnancy test performed within 28 days prior to initiation of the study & at the time of check-in of each period.
- •b)Acceptable forms of contraception include the following: i.Intrauterine device in place for at least 3 months prior to the start of the study and remaining in place during the study period, or ii.Barrier methods containing or used in conjunction with a spermicidal agent, or iii.Surgical sterilization, or iv.Practicing sexual abstinence throughout the course of the study c)Females will not be considered of childbearing potential if one of the following is reported and documented on the medical history: i.Postmenopausal with spontaneous amenorrhea for at least one year, or ii.Bilateral oophorectomy with or without a hysterectomy and an absence of bleeding for at least 6 months, or iii.Total hysterectomy and an absence of bleeding for at least 3 months 3)Life expectancy of at least 3 months.
- •Patients willing to not change their concurrent medications during the study.
- •All patients should have a Body Mass Index (BMI) less than or equal to 35 but greater than or equal to
- •BMI values should be rounded to the nearest integer.
- •(e.g. 35.4 rounds down to 35, while 17.5 rounds up to 18) 6)Able to comply with Protocol requirements and assessments 7)Able to give written informed consent to participate in the study 8)All patients should be judged eligible by the principal investigator or co-investigator or physician during a pre-study safety assessment performed within 28 days of the first dose of study medication which will include a)A complete medical history b)A normal or clinically non-significant physical examination.
- •c)Within normal limits or clinically non-significant laboratory evaluation results (unless otherwise noted in the exclusion criteria) for the following tests.
排除标准
- •Subject candidates must not be enrolled in the study if they meet any of the following criteria: 1.History of allergic responses to Capecitabine, or other related drugs and any of its formulation ingredients or 5-fluorouracil.
- •2.Patients receiving concomitant therapy of warfarin (coumarin anticoagulants) or history of usage of coumarin anticoagulants in the previous three months prior to study start (dosing).
- •3.Known history of dihydropyrimidine dehydrogenase deficiency 4.Consumption of grapefruit, grapefruit-like or grapefruit containing products within 7 days of drug administration.
- •5.Ingestion of any alcoholic, caffeine or xanthine containing food or beverage within the 48 hours prior to the initial dose of study medication.
- •6.Use of enzyme-modifying drugs within 30 days prior to receiving the first dose of study medication (listed in Appendix-II).
- •They can be allowed depending on Principal Investigator’s discretion in consultation with Medical monitor, if they are kept constant in the last 30 days and are expected to remain constant during the study period.
- •7.History of moderate (30-50 ml/min creatinine clearance) or severe (≤ 30 ml/min creatinine clearance) renal disease.
- •8.Impaired hepatic function (bilirubin ≥2.5 times the upper limit of normal, transaminases or alkaline phosphatase ≥ 2.5 times the upper limit of normal).
- •9.Major surgery to the gastrointestinal tract, the liver or kidney within 4 weeks of study entry which may impact on the pharmacokinetics of Capecitabine.
- •10.Participation in any investigational drug study within 30 days prior to period 1 dosing.
- •11.History of difficulty in swallowing, or any gastrointestinal disease which could affect drug absorption.
- •12.History of peptic ulcer, ulcerative colitis, ulcerative stomatitis and/or lack of physical integrity of the upper intestinal tract.
- •13.Patients with History of coronary artery disease.
- •14.Patients with prolonged QT or clinically significant ECG changes 15.Known, existing uncontrolled coagulopathy.
- •16.Donation or loss of blood or plasma of one unit (about 450 mL whole blood or 220 mL plasma) in the previous 60 days.
- •17.Any significant disease or condition which might compromise the haemopoeitic, gastrointestinal, renal, hepatic, cardiovascular, respiratory, central nervous system, diabetes, psychosis or any other body system.
- •19.Smokers, who smoke more than or equal to 10 cigarettes per day or more than or equal to 20 biddies per day or those who cannot refrain from smoking during study period.
- •20.History of difficulty with donating blood or difficulty in accessibility of veins or intolerance to venipuncture.
- •21.History of allergic response to heparin.
- •22.A positive hepatitis screen (includes subtypes B & C) 23.A positive test result for HIV antibody and / or syphilis (RPR/VDRL) 24.Any food allergy, intolerance, restriction or special diet that, in the opinion of the Principal Investigator or Sub-Investigator, could contraindicate the patient’s participation in this study 25.Any other condition that, in the investigator’s judgment, might increase the risk to the patient or decrease the chance of obtaining satisfactory data needed to achieve the objectives of the study.
结局指标
主要结局
To characterize the pharmacokinetic profile of the sponsor’s test formulation (Capecitabine Tablets 500 mg, Manufactured by Cadila Heathcare Limited, India) relative to that of reference formulation (XELODA® 500 mg tablets, Manufactured by Genentech USA Inc. USA) in patients of Metastatic Breast Cancer, Duke’s C Colon Cancer or Metastatic Colorectal Cancer under fed condition and to assess the bioequivalence.
时间窗: Time points are 30 minutes prior to drug dosing and at 0.25hr, 0.50hr, 1hr, 1.5hr, 2hr, 2.5hr, 3hr, 4hr, 5hr, 6hr, 8hr and 10 hours post-dose.
次要结局
- To monitor the safety of the patients(30 minutes prior to drug dosing and 0.25, 0.50, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8 and 10 hours post-dose.)