A Randomized Open label Single Dose Two Treatment Three Period Three Sequence Partial Replicate Crossover Multicentre Bioequivalence Study of Capecitabine Biopharm 500 mg film coated Tablets (Manufactured by Profam Algeria for Biopharm SPA Algeria) with XelodaÂ® 500 mg Film Coated Tablets Capecitabine (Manufacturer Excella GmbH and Co KG Germany and Marketing Authorisation Holder CHEPLAPHARM Arzneimittel GmbH Germany in Adult Cancer Patients Under Fed Conditions

BIOPHARM SPA9 个研究点分布在 1 个国家目标入组 72 人开始时间: 2024年6月13日最近更新: 2025年1月30日

试验速览

阶段: 不适用
状态: 招募中
发起方: BIOPHARM SPA
入组人数: 72
试验地点: 9
主要终点: 1 Bioequivalence of two formulations (Test vs Reference) in

研究概览研究设计入排标准结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

A randomized open-label single-dose two-treatment three-sequence three-period partial replicate crossover bioequivalence study. Patients with Dukesâ€™ C colon cancer metastatic colorectal cancer or metastatic breast cancer will be enrolled in the study Screening procedure will include collection of demography data, medical history physical examination, vital signs (pulse, blood pressure, respiratory rate and oral temperature), 12 lead electrocardiogram (ECG), chest X-ray, hematology, biochemistry, serology, urine pregnancy test (for female patients of childbearing potential), urinalysis and ECOG performance evaluation. During this three-period study, all patients will receive a single dose of the test product once and single dose of the reference product twice (reference replicate study design) under fed conditions. Each patient will be randomized to receive test and reference products as per any one of the three sequences according to the randomization schedule In each period, following an overnight fast of at least 10 hours, patients will be given high fat high calorie breakfast approximately 800-1000 Kcal) 30 minutes before investigational product administration. Patients will consume this breakfast in 30 minutes or less and the investigational product will be administered 30 minutes after start of the breakfast. Compliance to high-fat high calorie breakfast will be assessed by the site personnel and

will be documented. Patients will take 03 tablets of either the investigational product or reference administered at once with 200 mL of water after high fat and high calorie breakfast. Investigational

products (Test or Reference) must be swallowed whole and must not be chewed, crushed or divided. This activity will be followed by mouth and hand check of the patients to assess compliance to dosing.

The dose will be calculated based upon body surface area of patients. The recommended dose of capecitabine is 1250 mg/m2 administered orally twice daily (equivalent to 2500 mg/m2 total daily dose). The patients will be administered either the reference drug or the test drug only as the first morning dose. On Day 1 (Period I), patients will receive the morning dose of capecitabine as IP (test or reference). The remaining balance daily dose of the day (evening dose) will be administered after 12 hours of the morning dose as non IP. The evening dose will be calculated as â€˜Total daily dose minus Morning doseâ€™. On Day 2 (Period II) and Day 3 (Period III), patients will be crossed over to receive either test or reference products as per the randomization schedule. The morning dose (IP) and evening dose (non IP) of capecitabine will remain the same in all three study periods. From Day 4 of the cycle onwards, the patient will continue to receive his/ her twice-daily stable dose as per the schedule determined by Investigator. A washout period of at least 24 hours will be given between each dosing (Test or Reference)

研究设计

研究类型: Interventional
分配方式: Randomized
盲法: None

入排标准

年龄范围: 18.00 Year(s) 至 60.00 Year(s)（—）
性别: All

入选标准

•1 Males or non-pregnant or non-lactating females of age between greater than 18 to 60 years (both inclusive) 2 Patients in whom capecitabine therapy is indicated Dukesâ€™ C colon cancer Single agent as adjuvant therapy or Metastatic colorectal cancer First line as monotherapy when treatment with fluoropyrimidine therapy alone is preferred or Metastatic Breast Cancer As monotherapy in patients resistant to both paclitaxel and an anthracycline containing regimen 3 Patients already receiving a stable twice-daily dosing regimen of capecitabine (1250 mg/m2 twice daily equivalent to 2500 mg/m2 total daily dose for two-weeks followed by a one-week rest period given as three-week cycles) 4 Patients with Eastern Cooperative Oncology Group (ECOG) performance status â‰¤ 2 5 Patients with life expectancy of at least 3 months 6 Adequate cardiac function [left ventricular ejection fraction LVEF â‰¥ 50 % 7 Patient with adequate.
•Bone marrow (ANC â‰¥ 1500/mm3, Platelet count â‰¥ 100,000/mm3 Hemoglobin â‰¥ 9.0 g/dL).
•Renal (Serum Creatinine â‰¤ 1.5 times ULN and creatinine clearance â‰¥ 51 to 80 mL/min [Cockroft and Gault]) and.
•Hepatic function (Bilirubin â‰¤ 1.5 times ULN, ALT/AST â‰¤ 3 times ULN (â‰¤ 5 x ULN if liver metastases present)) 8 Patients should be non-smokers 9 Patient willing and able to give written informed consent for participation in the study and comply with the study protocol 10 No persistent clinically significant toxicities from prior medications at screening. 11 Females of child-bearing potential must agree to use an acceptable method of birth control such as sexual abstinence or at least reliable modes of contraception from screening until 3 months after last dose of study drug [Note Use of hormonal contraception(pills/hormonal intrauterine device etc) is not allowed OR Post-menopausal females defined as at least 12 consecutive months with no menses without an alternative medical cause OR surgically sterilized females with documented evidence of hysterectomy/bilateral salpingectomy/bilateral oophorectomy 12 Male patient must agree to use an acceptable method of birth control such as sexual abstinence or barrier method of contraception (condom) from screening until 3 months after last dose of study drug Subject agrees to accept the risk that pregnancy in female partner could still result despite using birth control devices 13 Cancer patients should preferably be on monotherapy However cancer patients receiving concomitant drug(s) are allowed to participate provided.
•The concomitant medication is the same for all the study period and clearly documented.
•Patients do not require any change in their concurrent medications during the study period.

排除标准

•1 Patients with known hypersensitivity to capecitabine or to any of its components of formulation or 5-fluorouracil 2 Patients with known DPD (Dihydro pyrimidine Dehydrogenase) deficiency 3 Prior unanticipated severe reaction to Capecitabine or metabolites and to fluoropyrimidine therapy 4 Patients with a prior history of coronary artery disease 5 Patients who are on oral-coumarin derivative anticoagulants such as warfarin or phenprocoumon at the time of screening or anticipated use of these drugs during the study period[If the subject was on any of these drugs before screening a wash out 19 Patient having abnormal serum calcium level at screening visit which as judged by Investigator could lead to safety risk to the patient upon participation in the trial or could interfere with the conduct of the trial period of at least 5 half-lives must have elapsed since the last dose of such drug 6 Patients receiving concomitant therapy of Phenytoin Leucovorin and CYP2C9 substrates at the time of screening or anticipated use of these drugs during the study period [If the subject was on any of these drugs before screening a wash out period of at least 5 half-lives must have elapsed since the last dose of such drug] Presence of active infections 7 Patients with known brain metastasis.
•8 Pre-existing motor or sensory neurotoxicity of severity â‰¥ 2 by National Cancer Institute Common Terminology Criteria for Adverse Event (NCI CTCAE) criteria 9 Use of any recreational drugs or history of drug addiction 10 Have a history of alcohol or drug-dependence as per DSM-IV criteria during the 6-month period immediately prior to Screening 11 Consumption of grapefruit grapefruit-like or grapefruit containing products within 7 days prior to study drug administration 12 Use of enzyme modifying drugs within 30 days prior to study drug administration They can be allowed depending on Principal Investigatorâ€™s discretion if they are kept constant in the last 30 days and are expected to remain constant during the study period 13 Major surgery to the gastrointestinal tract, liver or kidney within 3 months prior to study entry which may affect the pharmacokinetics of capecitabine 14 History of difficulty in swallowing or any gastrointestinal disease e.g. ulcerative colitis ulcerative stomatitis malabsorption syndrome and/or lack of physical integrity of the upper intestinal tract which could affect drug absorption 15 History or presence of cardiac disease including myocardial infarction unstable angina coronary artery disease heart failure dysrhythmias cardiomyopathy significant pericardial disease or any other cardiac illness that could affect patient safety 16 Electrocardiographic evidence of acute ischemic or active conduction system abnormalities 17 History or evidence of uncontrolled coagulopathy.
•18 Patients with severe hepatic or renal impairment 19 Patient having abnormal serum calcium level at screening visit which as judged by Investigator could lead to safety risk to the patient upon participation in the trial or could interfere with the conduct of the trial 20 Patients who have had experienced a severe mucocutaneous reaction during prior capecitabine treatment 21 History of difficulty with donating blood or difficulty in accessibility of veins or intolerance to venepuncture or patients who have bled more than 300 mL in the past 3 months 22 Participation in any clinical trial of investigational drugs or devices in the past 3 months 23 Any significant disease or condition of haemopoietic gastrointestinal renal hepatic cardiovascular respiratory central nervous system diabetes psychosis or any other body system which might compromise patient safety or affect study results 24 Patients with positive alcohol breath test or positive urine screen test for drugs of abuse (Amphetamines, Morphine Benzodiazepines Marijuana, Cocaine and Barbiturates) at Period I hospitalization 25 A positive screen test for HIV 1 and 2 or Hepatitis B (HBsAg) or Hepatitis C (HCV) virus 26 History of allergy to heparin or any food allergy that in the opinion of the Investigator could contraindicate the patientâ€™s participation in study 27 Any other condition that in the investigatorâ€™s judgment might compromise patient safety or affect study results.