A multicenter, open label, balanced, randomized, two-treatment, three-period, three sequence, single oral dose, partial replicate, cross-over, bioequivalence study comparing test formulation of capecitabine oral granules 500 mg per packet (Manufactured by: Intas Pharmaceuticals Ltd, India) to the reference formulation of Xeloda® (capecitabine) tablets 500 mg (Distributed by: Genentech USA, Inc., A member of the Roche group, 1 DNA Way, South San Francisco, CA 94080-4990) in patients with metastatic breast cancer or metastatic colorectal cancer, already receiving a stable twice-daily dose of 1250 mg/m2, equivalent to 2500 mg/m2 total daily dose under fed condition.
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 15
- 试验地点
- 5
- 主要终点
- [capecitabine oral granules 500 mg per packet (Manufactured by Intas Pharmaceuticals Ltd, India)] relative to that of reference formulation [Xeloda® (capecitabine) tablets 500 mg (Distributed by: Genentech USA, Inc., A member of the Roche group, 1 DNA Way, South san Francisco, CA 94080-4990)] in patients of metastatic breast cancer or metastatic colorectal cancer under fed condition and to assess the bioequivalence.
研究概览
简要总结
The present study is a bioequivalence study wherein the relative bioavailability of test formulation [capecitabine oral granules 500 mg (Manufactured by: Intas Pharmaceuticals Limited, India)] will be compared with reference formulation [Xeloda® (capecitabine) tablets 500 mg (Distributed by: Genentech USA, Inc., A member of the Roche group, 1 DNA Way, South san Francisco, CA 94080-4990] in patients with metastatic breast cancer or colorectal cancer under fed condition. Capecitabine is a cytotoxic drug. It would be unethical to do this study on healthy volunteers. Therefore the bioequivalence study is proposed to be carried out on patients of metastatic breast cancer or colorectal cancer, who in the opinion of their treating physicians are candidates for capecitabine therapy. Moreover, this is also in agreement with the current draft guidance on capecitabine by OGD, USFDA. The recommended dose of XELODA® is 1250 mg/m2 administered orally twice daily (morning and evening; equivalent to 2500 mg/m2 total daily dose) for 2 weeks followed by a 1-week rest period given as 3 week cycles. The dose of capecitabine can be reduced in case of toxicity as per the Prescribing information of XELODA®. In current study, test formulation of capecitabine oral granules 500 mg and reference formulation of capecitabine tablets 500 mg will be administered as a single dose as multiples of 500 mg on day 1, day 2 and day 3 morning dose as per randomization schedule. The evening dose on day 1, day 2 and day 3 will be locally approved and marketed capecitabine Tablets 500 mg. Locally approved and marketed capecitabine will also be provided for the remaining treatment cycle/s.
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 65.00 Year(s)（—）
- 性别
- All
入选标准
- •Patient and /or LAR willing to give written informed consent for participation in the trial.
- •Male or Female ≥18 years and ≤ 65 years of age and having a Body Mass Index (BMI) at least 17 calculated as weight in kg / height in m
- •Patients must have/have had histopathologically /cytologically confirmed breast cancer or colorectal cancer.
- •Patients with a.
- •Dukes C colon cancer patients who have undergone complete resection of the primary tumour when treatment with fluoropyrimidine therapy alone is preferred.
- •Metastatic colorectal carcinoma when treatment with fluoropyrimidine therapy alone is preferred.
- •Metastatic breast cancer resistant to chemotherapy regimens with paclitaxel and anthracycline-resistant or paclitaxel for patients in whom additional therapy with an anthracycline is not indicated.
- •Patients who require a daily dose of capecitabine monotherapy, who are stabilized on twice daily dosing for at least one cycle of chemotherapy before randomization and who are eligible to receive a dose of 2500 mg/m2/day.
- •Patients should have their BSA between 1.26-1.91 (Both inclusive).
- •Eastern Cooperative Oncology Group (ECOG) performance status ≤
- •Adequate cardiac function (left ventricular ejection fraction [LVEF] ≥50%).
- •Patient should have recovered from any toxic effects of previous chemotherapy as judged by the Investigator.
- •Patients with life expectancy of at least 3 months (as per the Investigators discretion).
- •Able to comply with study requirement in opinion of Investigator.
- •Able to give written informed consent for participation in the trial.
- •In case of female patient the serum pregnancy test at screening visit and urine pregnancy test at day 0 must be negative.
- •Sexually active women, unless surgically sterile (at least 6 months prior to Study drug administration) or postmenopausal for at least 12 consecutive months, must use an effective method of avoiding pregnancy (including oral, transdermal, or implanted contraceptives [any hormonal method in conjunction with a secondary method], intrauterine device, female condom with spermicide, diaphragm with spermicide, absolute sexual abstinence, use of condom with spermicide by sexual partner or sterile [at least 6 months prior to Study drug administration] sexual partner) for at least 4 weeks prior to study drug administration, during study and up to 180 days after the last dose of study drug.
- •Cessation of birth control after this point should be discussed with a responsible physician.
- •In case of male patients: Either partner or patient must use an effective method of avoiding pregnancy for at least 4 weeks prior to study drug administration, during study and up to 90 days after the last dose of study drug.
排除标准
- •Prior unanticipated severe reaction to fluoropyrimidine therapy, or known sensitivity to 5-fluorouracil, or known DPD (Dihydropyrimidine Dehydrogenase) deficiency.
- •Pregnant or breast-feeding female.
- •Any of the following cardiac conditions: Unstable angina.
- •Myocardial infarction within the past 6 months.
- •NYHA (New York State Heart Association) class II-IV heart failure.
- •Severe uncontrolled ventricular arrhythmias.
- •Clinically significant pericardial disease.
- •Electrocardiographic evidence of acute ischemic or active conduction system abnormalities.
- •Any other cardiac illness that could lead to a safety risk to the patient in case of enrolment in the study.
- •Known brain metastasis.
- •Pre-existing motor or sensory neurotoxicity of a severity ≥ grade 2 by NCI CTCAE criteria.
- •A positive hepatitis screen including hepatitis B surface antigen and HCV antibodies.
- •Patients with HIV infection.
- •Patients found positive on urine scan for drugs of abuse and/or breath test for alcohol consumption at screening or baseline.
- •The receipt of an investigational medicinal product or participation in other drug research study within a period of 30 days (or 5 half-lives, whichever is longer) prior to the first dose of investigational medicinal product for the current study.
- •Any other condition that, in the investigators judgment, might increase the risk to the patient or decrease the chance of obtaining satisfactory data needed to achieve the objectives of the study.
- •Abnormal baseline findings considered by the investigator to indicate conditions that might affect study endpoints.
- •Donation of blood (1 unit or 350 ml) within 90 days prior to receiving the first dose of investigational medicinal product for the current study.
- •Known, existing uncontrolled coagulopathy.
结局指标
主要结局
[capecitabine oral granules 500 mg per packet (Manufactured by Intas Pharmaceuticals Ltd, India)] relative to that of reference formulation [Xeloda® (capecitabine) tablets 500 mg (Distributed by: Genentech USA, Inc., A member of the Roche group, 1 DNA Way, South san Francisco, CA 94080-4990)] in patients of metastatic breast cancer or metastatic colorectal cancer under fed condition and to assess the bioequivalence.
时间窗: Pre-dose and 0.167, 0.333, | 0.500, 0.750, 1.000, 1.250, 1.500, 1.750, 2.000, 2.250, 2.500, 2.750, 3.000, 3.333, | 3.667, 4.000, 4.500, 5.000, 6.000, 7.000 and 8.000 hour post-dose
To characterise the pharmacokinetic profile of the sponsors test formulation
时间窗: Pre-dose and 0.167, 0.333, | 0.500, 0.750, 1.000, 1.250, 1.500, 1.750, 2.000, 2.250, 2.500, 2.750, 3.000, 3.333, | 3.667, 4.000, 4.500, 5.000, 6.000, 7.000 and 8.000 hour post-dose
次要结局
- Safety of the patients(Through out the study)