A randomized, open label, balanced, multicenter, two-treatment, two-period, two-sequence, two-way crossover, single dose, bioequivalence study with pharmacokinetic endpoints of Paclitaxel Protein-Bound Particles for Injectable Suspension (albumin-bound) 100 mg/vial at a dose of 260 mg/m2 with ABRAXANE® for Injectable Suspension (albumin--bound) 100 mg/vial at a dose of 260 mg/m2 in Breast cancer subjects after failure of combination chemotherapy for metastatic disease.
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 60
- 试验地点
- 15
- 主要终点
- To assess the bioequivalence by comparing PK parameters of Paclitaxel Protein-Bound Particles for Injectable Suspension (albumin-bound) 100 mg/vial at a dose of 260 mg/m2 with ABRAXANE® for Injectable Suspension (albumin--bound) 100 mg/vial at a dose of 260 mg/m2 in Breast cancer subjects after failure of combination chemotherapy for metastatic disease or relapse within 6 months of adjuvant chemotherapy under fasting condition
研究概览
简要总结
This a randomized, open label, balanced, multicenter,two-treatment, two-period, two-sequence, two-way crossover, single dose,bioequivalence study with pharmacokinetic endpoints of Paclitaxel Protein-BoundParticles for Injectable Suspension (albumin-bound) 100 mg/vialat a dose of 260 mg/m2of NingboShouzheng Medicinal Research Co., Ltd. with ABRAXANE® for InjectableSuspension (albumin--bound) 100 mg/vial at adose of 260 mg/m2 of Celgene Corporation, Summit, NJ 07901 in Breastcancer subjects after failure of combination chemotherapy for metastaticdisease or relapse within 6 months of adjuvant chemotherapy under fastingcondition
The Primary Objective is To assess the bioequivalence bycomparing PK parameters of Paclitaxel Protein-Bound Particles for InjectableSuspension (albumin-bound) 100 mg/vial at a dose of 260 mg/m2 of Ningbo Shouzheng Medicinal ResearchCo., Ltd. with ABRAXANE® for Injectable Suspension (albumin--bound) 100 mg/vial at a dose of 260 mg/m2of Celgene Corporation, Summit, NJ 07901 in Breast cancersubjects after failure of combination chemotherapy for metastatic disease orrelapse within 6 months of adjuvant chemotherapy under fasting condition
Uponrandomization, subjects will receive assigned study drug on Day 1 (Period 01)and Day 22 (Period 02) based on the randomization schedule (either Test (A) orReference (B)) at a dose of 260mg/m2 intravenously over 30minutesunder fasting conditions.
Statistical analysis will beperformed on the pharmacokinetic parameters using SAS® statisticalsoftware. The 90% confidence intervalof the relative mean (Geometric mean) of the test to reference formulation forLn-transformed Cmax, AUC0-t and AUC0-infshould be within 80.00% to 125.00% for unbound and total paclitaxel toestablish bioequivalence.
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
- Female
入选标准
- •Female subjects will be considered eligible for the study based on the following criteria:
- •Willing and able to provide voluntary informed consent and to follow the protocol requirements.
- •Females aged 18 to 65 years (both inclusive) having Body Mass Index BMI at least 17.00 calculated as weight in kg per height in m
- •Subjects with histopathologically or cytologically confirmed breast cancer
- •Subjects with breast cancer after failure of combination chemotherapy for metastatic disease or having relapse within 6 months of adjuvant chemotherapy.
- •(Prior therapy should have included an anthracycline unless clinically contraindicated)
- •Eastern Cooperative Oncology Group (ECOG) performance status Less or equal to
- •Life expectancy of at least 3 months at the time of enrolment.
- •Acceptable hematology status: a.
- •Hemoglobin greater or equal to 9.0 g per dL b.
- •Absolute neutrophil count ANC greater or equal to 1500 cells per mm3 c.
- •Platelet count greater or equal to 1, 00,000 cells per mm3
- •Acceptable liver function: a.
- •Alanine aminotransferase ALT Less or equal to 2.5 X ULN b.
- •Bilirubin less or equal to 1.5 X ULN d.
- •Alkaline phosphatase less or equal to 5 X ULN
- •Subjects with Creatinine clearance greater or equal to 60 mL per minute
- •Subjects with negative serum pregnancy test at screening and negative urine pregnancy test at Day
- •Women of child bearing potential (defined as women physiologically capable of becoming pregnant, unless they are using effective method of contraception during dosing of the investigational product) practicing acceptable methods of contraception.
- •Acceptable methods of contraception are a.
- •Hormonal method (including oral, vaginal ring, transdermal patch, implanted or injection) started at least 7 days prior to day 0 plus one barrier method (cervical cap, diaphragm, contraceptive sponge, vaginal spermicide, female or male condom b.
- •Intrauterine device IUD or intrauterine system IUD or IUS placed 7 days prior to day 0 c.
- •Two barrier method used together (cervical cap, diaphragm, contraceptive sponge, vaginal spermicide, male or female condom) d.
- •Male sterilization at least 6 months prior to the screening, should be the sole male partner for that subject) plus one additional contraception method (hormonal or barrier method) e.
- •Documented tubal sterilization (tubal ligation or transcervical tubal occlusion with documentation of occlusion 6 months post-procedure) f.
- •Total abstinence, partial abstinence is not acceptable (no sexual intercourse or genital contact with a male partner)
- •Female subjects of non-child bearing potential or female subjects who have completed menopause are defined as subjects who have 12 consecutive months of spontaneous amenorrhea (not amenorrhea induced by a medical condition or medical therapy) or have bilateral absence of the ovaries.
- •Female subjects of non-child bearing potential are not required to use effective method of contraception during the study 13.
排除标准
- •Female subjects will be excluded from the study based on the following criteria: 1.Known hypersensitivity to Paclitaxel or the components of Paclitaxel Protein-Bound Particles for Injectable Suspension (albumin--bound) or to any of the related drugs (other taxane products).
- •2.History or presence of any uncontrolled systemic disease (e.g. cardiovascular disease, hypertension, diabetes mellitus etc.).
- •3.Subjects taking any of the inhibitors or inducers of either CYP2C8 or CYP3A
- •(Appendix C) 4.Known CNS metastasis.
- •5.Major surgical procedure (including periodontal) within 28 days of first dose of Investigational Product.
- •6.Surgical or other non-healing wounds.
- •7.Subjects with positive serology for Hepatitis B Virus (HBV), Hepatitis C Virus (HCV), or Human Immunodeficiency Virus (HIV).
- •8.Subjects with current clinical or laboratory evidence of active infection.
- •9.History of other malignancies in the last 5 years (except in situ cancer or basal or squamous cell skin cancer).
- •10.Has not recovered to Grade 0 or 1 toxicity from previous anticancer treatments or previous investigational agents.
- •Exceptions are alopecia (any grade is acceptable), fatigue (Grade less than or equal to is acceptable), and peripheral neuropathy (stable Grade 2 is acceptable) (Per National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE], V5.0).
- •11.Participation in any clinical study within 90 days before the first dose of Investigational Product.
- •12.Loss of greater or equal to 350mL (1 unit) of blood within 90 days of enrollment in the study.
- •13.Any other medical condition or serious intercurrent illness that, in the opinion of the Investigator, may make it undesirable for the subject to participate in the study including but not limited to cirrhosis or psychiatric illness/social situations that would limit adherence to study requirements.
- •14.Subjects who are breastfeeding and lactating.
结局指标
主要结局
To assess the bioequivalence by comparing PK parameters of Paclitaxel Protein-Bound Particles for Injectable Suspension (albumin-bound) 100 mg/vial at a dose of 260 mg/m2 with ABRAXANE® for Injectable Suspension (albumin--bound) 100 mg/vial at a dose of 260 mg/m2 in Breast cancer subjects after failure of combination chemotherapy for metastatic disease or relapse within 6 months of adjuvant chemotherapy under fasting condition
时间窗: Day 1 and 22, 2 and 23, 3 and 24, 4 and 25, 5 and 26.
次要结局
- To monitor the adverse events and to assess the safety and tolerability in subjects.(Day 1 and 22, 2 and 23, 3 and 24, 4 and 25, 5 and 26.)