CTRI/2018/08/015335已完成1 期
A Multicentric Open Label Randomized Two Treatment Two-sequence Two period Cross-over Multiple dose, Steady-state Clinical Bioequivalence Study of Everolimus 10 mg tablets of Eugia Pharma Specialities Limited India A Joint venture of Aurobindo Pharma Limited and Celon Laboratories Limited Test with Afinitor® Everolimus 10 mg tablets of Novartis Pharmaceuticals Corporation USA Reference in advanced renal cell carcinoma patients under fasting conditions
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 42
- 试验地点
- 15
- 主要终点
- Cmax AUC0-Ï„ Area under the blood concentration time curve over the steady state dosing interval
研究概览
简要总结
There was allowed screening period of 21 days. This was a two period study without washout. Period I was from Day 1 to Day 14 and Period II was fromDay 15 to Day 28. Patients were administered one tablet of investigational medicinal product as per randomization schedule from Day 1 to Day 28.
Complete PK sampling was done on Day 14 and Day 28. Pre-dose blood sample of 3 mL was collected within 5 minutesbefore dosing on Day 1, 12, 13, 14, 15, 26, 27 and 28 to confirm steady state.On Day 14 and 28, venous blood samples of 3 mL was collected at 0.17, 0.25, 0.50, 0.75, 1.00, 1.25, 1.50, 1.75, 2.00,2.25, 2.50, 3.00, 4.00, 6.00, 8.00, 12.00, 16.00 and 24.00 hours post drugadministration.
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
- •1.Male and females of age in between 18 years to 65 years (both inclusive).
- •2.Ability to provide informed consent prior to participation in the study by patient/LAR 3.Confirmed diagnosis of advanced renal cell carcinoma.
- •4.Who are already receiving a stable dose of Everolimus tablets, 10 mg tablet once daily as per investigator’s discretion for at least 14 days at first dosing of study drug.
- •5.Eastern Cooperative Oncology Group (ECOG) performance status of 0-
- •6.Estimated life expectancy ≥ 3 months.
- •7.No persistent toxicities from prior medications [Recovery to baseline or ≤ Grade 1 CTCAE v.4.03 (or) higher and/or stable on supportive therapy at screening visit if any toxicities had occurred unless the toxicities were clinically insignificant] 8.Adequate organ and bone marrow function based upon the following laboratory criteria within 7 days before randomization: a.Hemoglobin ≥9.0 g/dL b.Absolute neutrophil count ≥1500/uL c.Platelet count ≥100,000/uL d.Creatinine < 1.5 x ULN e.Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 2.5 × upper limit of normal.
- •f.Total bilirubin within ≤ 1.5 × upper limit of normal.
- •g.Clinically insignificant fasting serum glucose levels, S.
- •blood urea nitrogen (BUN) and Urine protein levels.
- •9.Patient having negative urine screen for drugs of abuse 10.Patient having negative breath alcohol test 11.Sexually active women, unless surgically sterile (at least 6 months prior to study drug administration) or postmenopausal for at least 12 consecutive months, must agree to use effective methods of avoiding pregnancy from screening, during study and up to 8 weeks after the last dose of study drug.
- •12.Females must use acceptable and effective methods of contraception such as the following: •Tubal sterilization (tubal ligation performed more than one month before Study Day1 transcervical tubal occlusion procedure performed more than six months before Study Day 1) •Intrauterine Device (IUD) •Progestin Implant (i.e. Implanon or its equivalent) •Progestin injection or progestin oral contraceptive pill + one barrier method (cervical cap, diaphragm, contraceptive sponge, or vaginal spermicide + a male or female condom) •Two barrier methods used together (cervical cap, diaphragm contraceptive sponge, or vaginal spermicide + a male or female condom) •Absolute sexual abstinence (no sexual intercourse or genital contact with a male partner) 13.Male patient must agree to use an effective method of contraception from screening, during study and up to 8 weeks after the last dose of study drug.
- •14.Clinically insignificant laboratory values at screening 15.Patients willing to and able to comply with the protocol.
排除标准
- •1.Known hypersensitivity to rapamycin, temsirolimus, everolimus or any excipient of everolimus.
- •2.Any prior treatment with everolimus resulting in unacceptable toxicity.
- •3.Receipt of any type of small molecule kinase inhibitors (i.e. axitinib, pazopanib, sorafenib, sunitinib etc) within 2 weeks before randomization.
- •4.Patients with renal failure, hepatic failure or for whom the need for dose change during the study can be anticipated.
- •5.Radiation therapy for bone metastasis within 2 weeks, any other external radiation therapy within 4 weeks before randomization.
- •6.Patients on active treatment with strong, moderate inhibitors or strong inducers of P-glycoprotein and CYP3A4[a minimal of 2 weeks or 5 half- lives wash-out period(whichever is earlier) recommended after stopping such medications].
- •7.History of brain metastasis, spinal cord compression 8.Systemic treatment with radionuclides within 6 weeks before randomization or with clinically relevant persistent complications from prior radiation therapy.
- •9.Concomitant anticoagulation at therapeutic doses with oral anticoagulants or platelet inhibitors [Low-dose aspirin and low-dose warfarin (< 1 mg/day), are permitted].
- •Anticoagulation with low molecular weight heparin (LMWH) is allowed if on a stable dose for at least 2 weeks before randomization.
- •10.Uncontrolled, significant inter-current or recent illness including, but not limited to a.Cardiovascular disorders: i.Symptomatic congestive heart failure, unstable angina pectoris, serious cardiac arrhythmias.
- •ii.Uncontrolled hypertension defined as sustained BP 150 mm Hg systolic or > 100 mm Hg diastolic despite optimal antihypertensive treatment.
- •iii.Stroke (including TIA), myocardial infarction, within 6 months before randomization.
- •b.Gastrointestinal (GI) disorders including those associated with a high risk of perforation or fistula formation: i.
- •Active peptic ulcer disease, inflammatory bowel disease, diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, acute pancreatitis or acute obstruction of the pancreatic or biliary duct, or gastric outlet obstruction.
- •Clinically significant hematuria, hematemesis, or hemoptysis of half teaspoon (2.5 ml) of red blood, or other history of significant bleeding (eg, pulmonary hemorrhage) within 3 months before randomization.
- •c.Cavitating pulmonary lesion(s) or known endobronchial disease manifestation.
- •d.Patient with active infection and symptoms of Non-infectious pneumonitis as judged by the investigator.
- •e.Malabsorption syndrome.
- •f.Serious non-healing wound/ulcer/bone fracture.
- •g.Lesions invading major pulmonary blood vessels.
- •12.Pregnant and lactating females.
- •13.Chronic treatment with corticosteroids or other immunosuppressive agents (with the exception of inhaled or topical corticosteroids or corticosteroids with a daily dosage equivalent ≤ 10 mg prednisone if given for disorders other than renal cell cancer).
- •14.Positive test for hepatitis B surface antigen, hepatitis C antibody, or human immunodeficiency virus (HIV) 1 and 2 serological test at screening or has been previously treated for hepatitis B, hepatitis C or HIV infection.
- •15.Local or systemic clinically significant infection within 28 days of screening as determined by the investigator.
- •16.Patients within 4 weeks post-major surgery, open biopsy, or significant traumatic injury to avoid wound healing complications within 4 weeks prior to study or who have not recovered from prior major surgery or patient is anticipated to require major surgery during the course of the study.
- •17.Participation in another clinical trial in the last 60 days.
- •18.Clinically significant abnormal finding on the physical examination, medical history, ECG, Chest X ray or clinical laboratory results at screening according to the Principal Investigator precluding everolimus administration.
- •19.History of noncompliance to medical regimens.
- •20.History of alcoholism / alcohol abuse.
- •21.History of difficulty with donating blood or difficulty in accessibility of veins.
- •22.Patients for whom oral administration of drug is not possible.
- •e.g. religious fasting.
- •24.Consumption of grape fruit/mosumbi/sweet lime juice within 48 hours prior to study check-in and for the entire period of study 25.Donation of blood (1 unit or 350 ml) within 90 days prior to receiving the first dose of investigational medicinal product in the study.
- •26.Females of child bearing potential unwilling to use acceptable contraception throughout the trial and for 8 weeks after the last dose of study drug.
结局指标
主要结局
Cmax AUC0-Ï„ Area under the blood concentration time curve over the steady state dosing interval
时间窗: Venous blood samples 3mL will be withdrawn within 5 minutes prior to dosing on Day 1 12 13 and 14 Period I and Day 15 26 27 and 28 Period II to confirm steady state condition | Venous blood samples 3mL will be withdrawn on Day 14 and 28 at 0.17 0.25 0.50 0.75 1 1.25 1.50 1.75 2.00 2.25 2.50 3.00 4.00 6.00 8.00 12.00 16.00 and 24.00 hours post drug administration.
Cmax ss Maximum concentration over the steady state dosing interval
时间窗: Venous blood samples 3mL will be withdrawn within 5 minutes prior to dosing on Day 1 12 13 and 14 Period I and Day 15 26 27 and 28 Period II to confirm steady state condition | Venous blood samples 3mL will be withdrawn on Day 14 and 28 at 0.17 0.25 0.50 0.75 1 1.25 1.50 1.75 2.00 2.25 2.50 3.00 4.00 6.00 8.00 12.00 16.00 and 24.00 hours post drug administration.
次要结局
- Minimum concentration over the steady state dosing interval(Average concentration over the steady state dosing interval)
研究者
研究点 (15)
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