A Randomized Open-Label, Single-Dose, Crossover Study Evaluating The Pharmacokinetics And Pharmacodynamics Of Filgrastim Hospira Compared To U.S.-Approved Neupogen® (Amgen) Following Subcutaneous Administration To Healthy Volunteers
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 24
- 试验地点
- 2
- 主要终点
- Maximum serum filgrastim concentration (Cmax)
研究概览
简要总结
This is a study comparing two study drugs, Filgrastim Hospira and Neupogen®. Neupogen® is approved by the US Food and Drug Administration (FDA) to treat low numbers of specific kinds of white blood cells (WBC) known as neutrophils. This type of white cell is important in fighting infections. A low neutrophil count is known as neutropenia. Both drugs work by increasing the number of neutrophils that are produced in the body.
This is important for patients who have low neutrophils due to chemotherapy, other treatments such as bone marrow transplant or certain other conditions with symptoms/problems related to low neutrophil counts. The main aim of the study is to test how Filgrastim Hospira works in the body compared to Neupogen®.
详细描述
This is a randomized, open-label, single-dose, two-way crossover study evaluating the PK and PD equivalence following SC administration of test and reference product in healthy volunteers. The study will be conducted at a single Phase 1 unit.
After meeting the selection criteria, subjects will be randomly assigned to 1 of the 2 treatment sequences:
- Filgrastim Hospira (US) followed by US-approved Neupogen®
- US-approved Neupogen® followed by Filgrastim Hospira (US)
Subjects will receive one of the drugs in the first Period and the other drug in the other Period.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Provides written informed consent, approved by an Independent Ethics Committee (IEC)/Institutional Review Board (IRB) prior to any study related activities
- •Healthy male or female volunteers between 18 and 65 years of age (both inclusive)
- •Body mass index (BMI) between 19 and 30 kg/m2, inclusive, and body weight of not < 50 kg or > 100 kg
- •Non smoker (defined as a subject who has not smoked and has not used nicotine containing products for at least 3 months prior to study drug administration and has a negative urine screen for cotinine) at Screening
- •Female subjects of childbearing potential, and male subjects and their partners of childbearing potential, agree to pregnancy prevention throughout the duration of the study (through the Final Visit). Subjects and their partners must agree to use of an effective method of contraception, to avoid impregnation of females throughout the course of the study. Subjects using oral contraceptives must be on a stable regimen for at least 3 months prior to Screening. While the best way to avoid pregnancy is to abstain from sexual activity, adequate forms of contraception to be used include oral contraception, depot contraception, intrauterine device (IUD), and barrier contraceptive methods, such as condoms and barrier creams/contraceptive jellies, and spermicidals. Subjects and their partners who can become pregnant must use contraception while on study drug from admission to the Final Visit. Male subjects must also refrain from donating sperm from admission to the Final Visit
- •Agrees to abstain from alcohol consumption throughout duration of the study and has a negative urine for alcohol at Screening
排除标准
- •Any active systemic or immunologic disease or condition, including but not limited to the following general categories: cardiovascular/pulmonary, hepatorenal, or systemic infection, or lactation
- •Hematologic laboratory abnormalities including leukocytosis (defined as total leukocytes > 11,000/µL), leukopenia (defined as total leukocytes < 4000/μL), or neutropenia (defined as absolute neutrophil count [ANC] < 1500/µL) or thrombocytopenia (defined as platelet count of < 150/µL)
- •Clinically significant, as judged by the Investigator, vital sign, chest X-ray, or 12-lead ECG abnormality
- •History of biological growth factor exposure, including but not limited to filgrastim and other G-CSFs in the context of treatment, prophylaxis, peripheral blood stem cell mobilization, or previous investigational study setting
- •Drug sensitivity, allergic reaction to, or known hypersensitivity/idiosyncratic reaction to Escherichia coli-derived proteins, filgrastim, pegfilgrastim, other granulocyte colony-stimulating factors or any component of the product. Subjects with the rare heredity problem of fructose intolerance are excluded due to the excipient sorbitol
- •History of splenic rupture (or subject who is asplenic), pulmonary infiltrate or pneumonia, sickle cell disease, chronic neutropenia, thrombocytopenia, or vasculitis
结局指标
主要结局
Maximum serum filgrastim concentration (Cmax)
时间窗: 1 hour prior to dose administration and 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, and 48 hours after dose administration
Area under the effect curve for Absolute Neutrophil Count (ANC) (AUEC ANC)
时间窗: 1 hour prior to dose administration and 0.5, 1, 2, 4, 6, 8, 24, 48, 72, 96 and 120 hours after dose administration
Maximum observed ANC ( ANC max)
时间窗: 1 hour prior to dose administration and 0.5, 1, 2, 4, 6, 8, 24, 48, 72, 96 and 120 hours after dose administration
Area under the serum filgrastim concentration versus time curve from zero to infinity (AUC0-∞)
时间窗: 1 hour prior to dose administration and 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, and 48 hours after dose administration
次要结局
- Time to maximum serum filgrastim concentration (Tmax)(1 hour prior to dose administration and 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, and 48 hours after dose administration)
- Area under the serum filgrastim concentration versus time curve from time zero to the time of the last measurable concentration versus time curve from time zero to the time of the last measurable concentration (AUC0-t)(1 hour prior to dose administration and 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, and 48 hours after dose administration)
- Time to maximum ANC (Tmax[ANC])(1 hour prior to dose administration and 0.5, 1, 2, 4, 6, 8, 24, 48, 72, 96 and 120 hours after dose administration)
- Elimination half-life (t ½)(1 hour prior to dose administration and 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, and 48 hours after dose administration)
- Clearance (CL)(1 hour prior to dose administration and 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, and 48 hours after dose administration)
- Volume of distribution (Vd)(1 hour prior to dose administration and 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, and 48 hours after dose administration)