Single Center, Randomized, Double-blind, 3-Period, 3-Treatments, 3-Way Crossover Pharmacokinetics (PK)/Pharmacodynamics (PD) Trial to Assess PK, PD,Safety and Tolerability of MYL-1401H After Single Subcutaneous Injection at One Dose Level (2 mg) Comparing to an EU and US Marketed Drug Product (Neulasta®) in Healthy Volunteers.
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Mylan Inc.
- 入组人数
- 218
- 试验地点
- 2
- 主要终点
- Maximum Serum Concentration (Cmax) of pegfilgrastim
研究概览
简要总结
This is a single center, double-blind, randomized, comparative pharmacokinetic and pharmacodynamic study of MYL-1401H and Neulasta (from EU and US source) in Normal Healthy Volunteers.
详细描述
After successful screening, each subjects will be randomly allocated to one of the following six possible sequences, according a 1:1:1:1:1:1 randomization scheme:
Sequence_1: Treatment A -> Treatment B -> Treatment C ; Sequence_2: Treatment A -> Treatment C -> Treatment B ; Sequence_3: Treatment B -> Treatment A -> Treatment C ; Sequence_4: Treatment B -> Treatment C -> Treatment A ; Sequence_5: Treatment C -> Treatment A -> Treatment B ; Sequence_6: Treatment C -> Treatment B -> Treatment A ;
In study Period 1, Subjects will be administered MYL-1401H (Treatment A), EU-Neulasta(Treatment B) or US-Neulasta (Treatment C).
After the 1st crossover, subjects will enter Study period 2 and will receive one of the remaining alternate treatments.
After the 2nd crossover, subjects will enter Study period 3 and will receive the other alternate treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Health Services Research
- 盲法
- Triple (Participant, Care Provider, Outcomes Assessor)
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
- •Weight: ≥60 kg.
- •Body mass index (BMI): 19.0-30.0 kg/m2
- •Vital signs showing no clinically relevant deviations.
- •Computerized 12-lead ECG recording without signs of clinically relevant pathology.
- •Non-smoker or light smoker
- •Ability and willingness to abstain from alcohol from 48 hours prior to each admission to the clinical research center and prior to ambulatory visits, and during the stays in the clinic.
- •Fertile males and females participating in heterosexual sexual relations: willingness to use adequate contraception from screening until 90 days after the follow up visit
- •Females must not be lactating and must have a negative pregnancy test at screening and each admission.
- •ANC, total leukocyte count, platelet count, hematocrit and hemoglobin results within the reference ranges.
- •All other values for hematology and for clinical chemistry tests of blood and urine within the normal range or showing no clinically relevant deviations as judged by the Principal Investigator
- •Other protocol specific inclusion/exclusion criteria may apply
排除标准
- •Unable to follow protocol instructions in the opinion of the Principal Investigator.
- •Any past or concurrent medical conditions that potentially increase the subject's risks or affect the evaluation of any study results. Examples of these include medical history with evidence of clinically relevant pathology (e.g. sickle cell disorders, spleen pathologies, hematologic malignancies or myelodysplastic disorders, and pulmonary illnesses such as ARDS, interstitial pneumonia, pulmonary edema, pulmonary infiltrates and pulmonary fibrosis) and history of relevant drug and/or food allergies.
- •Known history of previous exposure to filgrastim, pegfilgrastim, granulocyte colony stimulating factor (GCSF) or any analogue of these.
- •Hypersensitivity to the constituents of Neulasta® (sorbitol E420, polysorbate 20 and acetate or acetic acid) or hypersensitivity to E. coli derived proteins.
- •Any infection, cough or fever within 1 week prior to first study drug administration.
- •Fructose intolerance.
- •First degree relatives with hematological malignancy.
- •Treatment with non-topical medications within 5 days prior to first admission to the clinical research center, with the exception of hormonal contraceptives, multivitamins, vitamin C, food supplements and a limited amount of paracetamol (acetaminophen), which may be used throughout the study.
- •Participation in a drug study within 60 days prior to study drug administration.
- •Donation or loss of more than 500 mL of blood over a period of 60 days prior to study drug administration. Donation of more than 1.5 L of blood (for men) / more than 1.0 L of blood (for women) in the 10 months preceding the start of this study.
- •History of alcohol abuse or drug addiction
- •Regular intake of more than 24 units of alcohol per week (one unit of alcohol equals approximately 250 mL of beer, 100 mL of wine or 35 mL of spirits).
- •Positive drug screen (opiates, methadone, cocaine, amphetamines (including ecstasy), cannabinoids, barbiturates, benzodiazepines, tricyclic antidepressants and alcohol).
- •Positive screen on hepatitis B surface antigen (HBsAg), anti-hepatitis C virus (HCV) antibodies, or anti-human immunodeficiency virus (HIV) 1/2 antibodies.
- •Other protocol specific inclusion/exclusion criteria may apply
结局指标
主要结局
Maximum Serum Concentration (Cmax) of pegfilgrastim
时间窗: Day 1 (0.5, 1, 2, 4, 6, 8, 10, 12, 20 h), Days 2, 3, 4, 5, 6, 7, 8, 9, 12, 15, 22, 29
Pharmacokinetics as measured by peak serum concentration of Pegfilgrastim
Pharmacodynamics: Area under the curve above baseline of ANC [ANC_AUC(0-tlast)]
时间窗: Day 1 (0.5, 1, 2, 4, 6, 8, 10, 12, 20 h), and on Days 2, 3, 4, 5, 6, 7, 8, 9, 12, 15, 22, 29
Area under the serum concentration-time curve (AUC0-inf) of Pegfilgrastim
时间窗: Day 1 (0.5, 1, 2, 4, 6, 8, 10, 12, 20 h), Days 2, 3, 4, 5, 6, 7, 8, 9, 12, 15, 22, 29
Pharmacokinetics as measured by total AUC after extrapolation from time t to time infinity
Pharmacodynamics: Maximum change from baseline in absolute neutrophil count (ANC); ANC_Cmax
时间窗: Day 1 (0.5, 1, 2, 4, 6, 8, 10, 12, 20 h), Days 2, 3, 4, 5, 6, 7, 8, 9, 12, 15, 22, 29
次要结局
- Safety Variable - Immunogenicity as measured by presence of Anti Drug Antibodies(Day 1 each period and at follow-up (Day 84))
- Frequency of Adverse Events(Daily until Day 9, then on Day 12, 15, 22 of each study period, and at follow-up visit (day 84).)
- Safety Variable - Tolerability as measured by Injection Site reactions(Daily until Day 5 of each period)