Single-Dose Fed Bioequivalence Study of Capecitabine Tablets (500 mg; Mylan) to Xeloda® Tablets (500 mg; Genentech) in Adult Cancer Patients with Metastatic Breast Cancer, Duke’s C Colon Cancer or Metastatic Colorectal Cancer.
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 42
- 试验地点
- 10
- 主要终点
- To characterize the pharmacokinetic profile of the sponsor’s test formulation (Capecitabine Tablets 500 mg, Manufactured by Mylan Pharmaceutical Inc., USA) relative to that of reference formulation (XELODA® 500 mg tablets, Manufactured by Genentech US 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 Mylan’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 forty-two (42) 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 10 hours prior to the first dose of investigational product until at least 12 hours after the final dose of investigational product. Blood samples (1×4 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 ± 5°C or colder until shipment to the central storage site. 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 80.00 Year(s)（—）
- 性别
- All
入选标准
- •1.Volunteers must be receiving stable doses of capecitabine (e.g. 2500 mg/m2/day in two divided dose) for the treatment of metastatic breast cancer (in combination with docetaxel), Dukes’ C colon cancer following complete resection, and metastatic colorectal carcinoma in combination with capecitabine (e.g. 2500 mg/m2/day in two divided doses).
- •a.Patients must have completed at least one 21-day cycle of capecitabine (i.e. 14 days of capecitabine and 7 days washout) at the dose to be utilized in this study.
- •b.The dose of capecitabine must be administered as a multiple of the intact, unbroken, 500 mg tablet.
- •2.Cancer patients with monotherapy are preferred.
- •However, cancer patients receiving concomitant drug(s) are allowed to participate, provided: a.The concomitant medication is the same during all study days.
- •Each concurrent medication will be documented and clearly identified.
- •Information recorded will include at least the following information: generic name, strength, dosing regimen, and time of dosing.
- •b.The subjects will follow the same dosing regimen for the concurrent medications for all dosing of the bioequivalent study.
- •c.Patients will not change their concurrent medications during the BE study.
- •d.Prior to inclusion of the subject into the study, a list of all concurrent medications will be provided to the sponsor for approval.
- •1.3.Age:18 – 80 years of age (inclusive) 2.4.Sex:Females of non-childbearing potential and Males (with equal numbers of each sex, if possible).
- •a.Women 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 (1) 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.
- •b.Non-lactating (or not nursing) 5.Capable of informed consent.
- •6.Weight Restrictions: a.At least 50 kg (110 lbs) for men and b.At least 48 kg (106 lbs) for women c.All subjects will 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 (ex.
- •7.Tobacco Use: Non-smokers to moderate-smokers (< 20 cigarettes per day) will be eligible to participate in this study.
- •8.All subjects should be judged by the principal or Medical Sub-Investigator physician listed on the Form FDA 1572 as normal and healthy during a pre-study medical evaluation performed within 28 days of the initial dose of study medication which will include: a.Normal or non-clinically significant physical examination including vital signs (respiration rate, blood pressure, temperature and heart rate).
- •b.Within normal limits or non-clinically significant laboratory evaluation results, (unless otherwise noted in the exclusion criteria), for the following tests: i.Serum Chemistries ii.Hematology iii.Urinalysis c.negative Hepatitis B and Hepatitis C tests, d.negative HIV test, e.INR within normal range f.normal or non-clinically significant 12-lead ECG g.negative urine drug screen for all of the following compounds: amphetamines, barbiturates, benzodiazepines, cannabinoid, cocaine, methadone, opiates, and phencyclidine.
- •9.Additional tests and or examinations may be performed, if judged necessary by the Principal Investigator or Medical Sub-Investigator physician.
排除标准
- •Subject candidates must not be enrolled in the study if they meet any of the following criteria: 1.Institutionalized subjects will not be used.
- •2.Individuals with dihydropyrimidine dehydrogenase (DPD) deficiency.
- •3.Individuals with rapidly progressing disease, especially with visceral organ involvement.
- •4.Individuals requiring a change in dose or regimen of either capecitabine or had their dosing regimen altered within the previous 21 days.
- •5.Social Habits: a.Ingestion of any alcoholic, caffeine- or xanthine-containing food or beverage within the 48 hours prior to the initial dose of study medication.
- •b.Ingestion of any vitamins, food, or herbal supplement known to induce or inhibit hepatic enzyme activity within 7 days prior to the initial dose of study medication.
- •Especially those known to inhibit or induce CYP3A
- •6.Medications: a.Use of warfarin currently or within the last 3 months.
- •b.Use of any prescription or over-the-counter (OTC) medications within the 24 hours prior to the initial dose of study medication, except for any necessary medication for which dosing has been stabilized for a period of at least 21 days and is expected to remain stable for the entire study.
- •c.Use of any medication known to induce or inhibit hepatic enzyme activity within 28 days prior to the initial dose of study medication except for any necessary medication for which dosing has been stabilized for a period of at least 28 days and is expected to remain stable for the entire study.
- •7.Diseases: a.History of unstable or clinically significant gastrointestinal disease, including a history of chronic diarrhea, inflammatory bowel disease, unresolved gastrointestinal symptoms (e.g. diarrhea, vomiting).
- •History of difficulties in swallowing.
- •b.ALT and AST greater than 2.5 times the upper limit of normal and/or total bilirubin greater than 2.5 times the upper limit of normal.
- •c.Patients with significant hepatic or renal dysfunction, or for whom the need for dose changes during the study can be anticipated.
- •d.Patients with a prolonged QT e.Known history of prior tuberculosis infection, or any contact within the past 2 years with person with active tuberculosis.
- •f.History of moderate (30-50 mL/min creatinine clearance) or severe (≤ 30 mL/min creatinine clearance) renal disease.
- •g.History of unstable or clinically significant cardiovascular disease, hepatic, pulmonary, hematologic, endocrine, immunologic, dermatologic, neurologic (including any history of seizure disorder), psychological, musculoskeletal disease or malignancies unless deemed not clinically significant by the Principal Investigator or Medical Sub-Investigator.
- •h.Acute illness at the time of either the pre-study medical evaluation or dosing.
- •8.Any reason which, in the opinion of the Principal Investigator or Medical Sub-Investigator, would prevent the subject form safely participating in the study.
- •9.Donation or loss of blood or plasma: 50 mL to 499 mL within 30 days prior to the initial dose of the study medication; or more than 499 mL within 56 days prior to the initial dose of study medication.
- •10.Intolerance to venipuncture.
- •11.Subjects who have received an investigational drug within 30 days prior to the initial dose of study medication.
- •12.History of allergy or hypersensitivity to capecitabine, or other related products, or any of the inactive ingredients.
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 Mylan Pharmaceutical Inc., USA) relative to that of reference formulation (XELODA® 500 mg tablets, Manufactured by Genentech US 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: NIL
次要结局
- To monitor the safety of the patients(Period one, two and three of the cycle)