A Randomized, Double-Blind Study to Assess the Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability of Single Subcutaneous Administration of Lipegfilgrastim (Doses up to 100 μg/kg) in Healthy Japanese and Caucasian Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Merckle GmbH
- 入组人数
- 48
- 试验地点
- 1
- 主要终点
- Apparent total body clearance (CL/F)
研究概览
简要总结
Cohorts of Japanese participants will be enrolled and treated prior to cohorts of Caucasian participants for the sake of matching. Every effort will be made to match Caucasian and Japanese participants on a cohort basis at enrollment. Reasonable effort will be made to maintain balance between male and female participants within the cohorts. There will be no replacement of participants following randomization.
详细描述
Eligible participants will be admitted to the investigational center and after confirming their eligibility will be randomized to receive a single dose of 30, 60, or 100 μg/kg lipegfilgrastim. There will be 11 visits to the investigational center during the study, including a screening visit, 1 inpatient period (through Day 4 post-dose) and 9 ambulatory visits.
Blood samples for PK, PD and immunogenicity analysis will be collected pre-dose and at specified time points post-dose. A mandatory blood sample for pharmacogenetics (PGx) will be collected from all participants. During the study the following safety assessments will be performed: vital signs measurements,physical examinations, record of adverse events, clinical laboratory tests, urinalysis, safety ECG recordings, local tolerability (injection site reactions), overall tolerability, pregnancy testing, spleen sonography, and concomitant medications
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 20 Years 至 45 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Body mass index (BMI) ≥18.0 and ≤25 kg/m
- •Body weight must be ≥ 50 kg and ≤ 90 kg.
- •Is in good general health as determined by medical history, physical examination, 12-lead electrocardiography (ECG), vital signs and clinical laboratory tests.
- •Subjects are able to read, write and understand English or Japanese; they must be able to understand the requirements of the study and be willing to comply with all trial requirements.
- •Female subjects of childbearing potential must have a negative serum β-human chorionic gonadotropin (β-hCG) test at screening and negative urine pregnancy test at check-in. All subjects must be either surgically sterile (for females that means documented complete hysterectomy, bilateral oophorectomyor bi-tubal ligations; partial hysterectomy is not sufficient), abstinent throughout the study or, if of reproductive capacity and not abstinent, exercising any 2 different forms of highly effective contraception methods with his/her partner during the entire study period.
- •o Additional inclusion criteria for Japanese subjects:
- •Subject must be a non-naturalized Japanese citizen and hold a Japanese passport.
- •Subject must have/had 2 Japanese parents and 4 Japanese grandparents who are all non-naturalized Japanese citizens, as confirmed by interview.
- •Subject has been living outside of Japan for 10 years or fewer as confirmed by interview.
- •o Additional inclusion criterion for Caucasian subjects:
- •The subject is Caucasian, and confirms by interview that his/her parents and grandparents are Caucasian and none are of Black/African descent, Middle-Eastern descent or Asian descent.
- •-other criteria apply, please contact the investigator for more information
排除标准
- •History of hypersensitivity to pegfilgrastim, filgrastim, lenograstim, Escherichia coli derived proteins, or to any excipients (glacial acetic acid, sodium hydroxide, sorbitol, polysorbate 20).
- •Prior exposure to filgrastim, pegfilgrastim or lenograstim or other granulocyte colony stimulating factors (G-CSFs) in clinical development less than 6 months before randomization.
- •Findings of splenomegaly on sonography, defined by splenic length in excess of 12.3 cm (Andrews, 2000; Benter et al, 2011) and clinical judgment.
- •Existence or recent history of persistent pulmonary infiltrates or recent pneumonia, or current symptoms of upper respiratory infection. In the case of pneumonia, subject may be screened 12 weeks following cessation of antibiotic treatment.
- •-other criteria apply, please contact the investigator for more information
研究组 & 干预措施
lipegfilgrastim 30
干预措施: lipegfilgrastim (Drug)
lipegfilgrastim 60
干预措施: lipegfilgrastim (Drug)
lipegfilgrastim 100
干预措施: lipegfilgrastim (Drug)
结局指标
主要结局
Apparent total body clearance (CL/F)
时间窗: Days 1-8, 10, 14, 17, 21
AUC from time 0 extrapolated to infinity (AUC0-∞)
时间窗: Days 1-8, 10, 14, 17, 21
Associated elimination half-life (t½)
时间窗: Days 1-8, 10, 14, 17, 21
Time to maximum observed serum drug concentration (tmax)
时间窗: Days 1-8, 10, 14, 17, 21
The percentage of the extrapolated area to infinity in relation to the total area under the curve (%AUCext)
时间窗: Visits 3, 9, 10
Apparent serum terminal elimination rate constant (λz)
时间窗: Days 1-8, 10, 14, 17, 21
2 hours for visits 3, 9; 1 day for visit 10
PK: Area under the serum concentration-time curve (AUC), from time 0 to the last measurable concentration (AUC0-t)
时间窗: Days 1-8, 10, 14, 17, 21
2 hours for visits 3, 9; 1 day for visit 10
Maximum observed serum drug concentration (Cmax)
时间窗: Days 1-8, 10, 14, 17, 21
Mean residence time (MRT)
时间窗: Days 1-8, 10, 14, 17, 21
Apparent volume of distribution during the terminal phase (Vz/F)
时间窗: Days 1-8, 10, 14, 17, 21
PD: ANC area over baseline effect curve (ANC AOBEC)
时间窗: Days 1-8, 10, 14, 17, 21
Maximum measured ANC value after dosing (ANC Cmax)
时间窗: Days 1-8, 10, 14, 17, 21
Time point at which ANC Cmax is observed (ANC tmax)
时间窗: Days 1-8, 10, 14, 17, 21
Time (days) until ANC returns to baseline value
时间窗: Days 1-8, 10, 14, 17, 21
CD34+ area over the baseline effect curve (CD34+ AOBEC)
时间窗: Days 1-8, 10, 14, 17, 21
Maximum measured CD34+ value after dosing (CD34+ Cmax)
时间窗: Days 1-8, 10, 14, 17, 21
Time point at which CD34+ Cmax is observed (CD34+ tmax)
时间窗: Days 1-8, 10, 14, 17, 21
次要结局
- Percentage of Participants with Adverse Events(28 Days)