A multicentric, open label, multiple dose, balanced, randomized, two-treatment, two-period, twosequence,full replicate, cross over study to evaluate bioequivalence of Etoposide Capsules 100 mg(Intas Pharmaceuticals Ltd., India) with Vepesid Soft Capsules 100 mg (Bristol-Myers Squibb S.r.lItaly) in patients with metastatic small cell lung cancer (SCLC) under fasting conditions.
试验速览
- 阶段
- 不适用
- 状态
- Other
- 入组人数
- 50
- 试验地点
- 15
- 主要终点
- Comparision of the bioequivalence and characterize the pharmacokinetic profile of the Sponsor formulation- Etoposide Capsules 100 mg (Intas Pharmaceuticals Ltd.,
研究概览
简要总结
This will be a multicentre, randomized, open label, two-period, two-treatment, two-period, two-sequence, full replicate, cross over study to evaluate bioequivalence of Etoposide Capsules 100 mg (Intas Pharmaceuticals Ltd., India)
with Vepesid Soft Capsules 100 mg (Bristol-Myers Squibb S.r.l Italy) in patients with metastatic small cell lung cancer (SCLC) under fasting conditions. Adult patient with small-cell lung cancer who are already receiving oral etoposide treatment and require at least 2 more cycles of oral etoposide treatment at steady dose will be enrolled into the study. In this study, 50 patients will be enrolled. Etoposide belongs to the group of medicines called cytostatics which are used in the treatment of cancer. Therefore the comparative bioequivalence study is proposed to be carried out in patients of metastatic small-cell lung cancer, who are already taking oral etoposide medication and expected to receive it for 2 more consecutive cycles. As per SMPC the recommended dose of etoposide is 100-200 mg per meter square administered orally once daily (morning dose) for 5 days followed by next cycle after 21-days. In each period of 5 days, patients will receive either test or reference formulation of etoposide capsule (2 x 100 mg) once daily in the morning in a crossover manner. After the study is completed, patients will be continued on their current dose of etoposide with available marketable formulations. Patient will be housed for 6 nights in each period during the study. The patient may be housed in the clinical facility (Hospital) for the entire duration of the study if in the opinion of the Investigator, this facilitates the study procedures. The Investigator will have to document this decision in the patient source document (like patient hospital records). Washout period of at least 16 days will be allowed during the study. Incidence of drug related Adverse Events will be assessed by clinical examination, vitals and/or laboratory parameters for both the treatments.
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
- •Male and female patients between 18 and 65 years of age (both inclusive).
- •Patients with confirmed metastatic small cell lung cancer.
- •Patients who are already receiving etoposide and expected to receive at least two additional cycles at the same dose.
- •Patients between BSA of 1.26 m2 and 2.00 m2 (both inclusive) who have received etoposide in the dose of 200mg once daily for 5 days and cisplatin 25mg/m2 administered on days 1, 2 and 3 in the previous cycle and are expected to receive same (200mg once daily (days 1-5) for etoposide and 25mg/m2 daily (days 1-3) for cisplatin) doses for the next 2 consecutive cycles (i.e. during the course of the study)
- •Eastern Cooperative Oncology Group (ECOG) performance status ≤
- •Patient with adequate bone marrow (without supplemental blood products/haematopoietic growth factors), renal and hepatic function.
- •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.
- •Able to comply with study requirement in opinion of Principal Investigator.
- •Patient 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 1 must be negative.
- •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 6 months after the last dose of study drug.
- •Cessation of birth control after this point should be discussed with a responsible physician.
- •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 6 months after the last dose of study drug.
排除标准
- •Patients who have demonstrated a previous hypersensitivity to the IMP or any component of the formulation.
- •Patients who have received more than 4 cycles of etoposide in the past.
- •Patients with history of Tumour lysis syndrome
- •Patients with ongoing significant active infection.
- •History of prior malignancy, with the exception of curatively treated squamous cell or basal carcinoma of the skin or in situ cervical cancer, unless there is a 3-year disease-free interval.
- •Creatinine clearance less than or equal to 50 mL/min
- •Patients with Daily dosing requirement greater than 200 mg etoposide.
- •Pregnant or breast-feeding female patients.
- •History of drug/alcohol addiction in past one year.
- •Known symptomatic brain metastasis
- •Patients receiving or expected to receive radiotherapy along with chemotherapy.
- •A positive hepatitis screen including hepatitis B surface antigen and HCV antibodies, or HIV infection.
- •Patients received any other chemotherapy, surgery or radiotherapy within 4 weeks before randomization or who have not recovered from side effects of such therapy.
- •Uncontrolled hypertension.
- •Patients with history of hypertension must be well controlled (≤140/90) on a stable regimen of anti-hypertensive therapy.
- •Concomitant use of CYP3A4 inhibitors.
- •Patients with massive pleural effusion, ascites and/or pericardial effusion
- •The receipt of an investigational medicinal product or participation in other drug research study within a period of 60 days prior to the first dose of investigational medicinal Product for the current study.
- •Clinically significant cardiac, neurological, psychiatric condition or any other condition that, in the investigator 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 or patient safety.
- •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.
结局指标
主要结局
Comparision of the bioequivalence and characterize the pharmacokinetic profile of the Sponsor formulation- Etoposide Capsules 100 mg (Intas Pharmaceuticals Ltd.,
时间窗: For Pre-dose | Day 01, Day 02, Day 03, Day 04, Day 22, Day 23, Day 24 and Day 25 | For Post dose | 0.167, 0.333, 0.500, 0.750, 1.000, 1.333, 1.667, 2.000, 2.333, 2.667, 3.000, 3.500, 4.000, 5.000, 6.000, 8.000, 10.000, 12.000, 16.000, 20.000 and 24.000 hours on day 04, day 05, day 25 and day 26.
India) with reference formulation Vepesid Soft Capsules 100 mg (Reference drug, Bristol-Myers Squibb S.r.l Italy).
时间窗: For Pre-dose | Day 01, Day 02, Day 03, Day 04, Day 22, Day 23, Day 24 and Day 25 | For Post dose | 0.167, 0.333, 0.500, 0.750, 1.000, 1.333, 1.667, 2.000, 2.333, 2.667, 3.000, 3.500, 4.000, 5.000, 6.000, 8.000, 10.000, 12.000, 16.000, 20.000 and 24.000 hours on day 04, day 05, day 25 and day 26.
次要结局
- safety of the patients who are exposed to the investigational(medicinal product.)