A Multicenter, Randomized, Open-Label, Parallel Group Phase 1 Pharmacokinetic Comparability Study of Benralizumab Administrated Using Accessorized Pre-Filled Syringe (APFS) or Autoinjector (AI) in Healthy Volunteers.
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 180
- 试验地点
- 2
- 主要终点
- Area Under the Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast)
研究概览
简要总结
An open-label, single dose Pharmacokinetic (PK) comparability study to demonstrate comparable drug exposure following Subcutaneous benralizumab administration by using accessorized pre-filled syringe (APFS) or autoinjector (AI) devices.
详细描述
A study of descriptive comparison of benralizumab PK by weight and injection site.
This study will be a multicenter, randomized, open-label, parallel group Phase 1 study designed to compare benralizumab PK exposure in healthy subjects following single subcutaneous (SC) administration of fixed 30 mg dose of benralizumab by using APFS and single-use AI. Eligible subjects will be healthy subjects aged 18 to 55 years, with a body weight of 55 to 100 kg and a body mass index of 18 to 29.9 kg/m2 . A total of 180 subjects will be randomized. Randomization will be stratified by weight group (55 to 69.9 kg, 70 to 84.9 kg and 85 to 100 kg), and within each of the 3 weight groups, subjects will be randomized 1:1:1:1:1:1 to 1 of the 6 combinations of treatment (APFS or AI) with injection site (upper arm, abdomen or thigh), presented in Table 1. This study will be performed at 2 study centers.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy male and/or female subjects of non-child-bearing potential aged 18 to 55 years (inclusive) with suitable veins for cannulation or repeated venipuncture.
- •Females must be non pregnant,non lactating and non-child-bearing potential, confirmed at screening
- •Sexually active male willingness to use contraception
- •Body mass index (BMI) between 18 and 29.9 kg/m2 inclusive and weigh at least 55 kg and no more than 100 kg inclusive.
排除标准
- •History of any clinically significant disease, severe allergy/anaphylaxis to any biologic therapy, Guillain-Barré syndrome, smoking and alcohol or drug abuse
- •Diagnosis of helminth parasitic infection and acute upper or lower respiratory infections
- •Disorders related to cardiovascular, gastrointestinal, hepatic, renal, neurological, musculoskeletal, infectious, endocrine, metabolic, hematological, psychiatric, or major physical impairment
- •Alanine aminotransferase/aspartate aminotransferase level ≥1.5 times the upper limit of normal
- •White blood cell count and neutrophils < lower limit of normal
- •Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of Investigational medicinal product (IMP)
- •Positive result for serum hepatitis B surface antigen or anti-Hemoglobin C (anti-HBc) antibody, hepatitis C antibody, and human immunodeficiency virus (HIV) antibody.
- •Intake of new chemical entity (not been approved for marketing) within 3 months of the first administration of investigational product
- •Plasma donation within 1 month of screening or any blood donation/loss more than 500 mL during the 3 months prior to screening
- •Receipt of immunoglobulin or blood products within 30 days prior to the date informed consent
- •Receipt of any marketed (e.g., omalizumab, mepolizumab etc.) or investigational biologic within 4 months or 5 half-lives prior to the date informed consent
- •Receipt of live attenuated vaccines 30 days prior to randomization on Day 1
- •Current malignancy, or history of malignancy except (basal cell carcinoma, localized squamous cell carcinoma of the skin or in situ carcinoma of the cervix)
- •Use of drugs with enzyme-inducing properties such as St John's Wort within 3 weeks prior to the first administration of IMP.
- •Use of antacids, analgesics (except paracetamol/acetaminophen), herbal remedies, mega-dose vitamins (20 to 600 times the recommended daily dose) and minerals during the 2 weeks prior to the first administration of IMP or longer
- •Previous receipt of received benralizumab
- •Any ongoing or recent minor medical complaints
- •Vulnerable subjects, e.g., kept in detention, protected adults under guardianship, trusteeship, or committed to an institution by governmental or juridical order
研究组 & 干预措施
Benralizumab by Autoinjector
Drug administration by Autoinjector A total of 180 subjects will be randomized and will be stratified by weight group (55 to 69.9 kg, 70 to 84.9 kg and 85 to 100 kg). Within each of the 3 weight groups, subjects will be randomized 1:1:1:1:1:1 to 1 of the 6 combinations of treatment (APFS) with injection site (upper arm, abdomen or thigh)
干预措施: Benralizumab (Biological)
Benralizumab by Accessorized Pre-Filled Syringe
Drug administration by Accessorized Pre-Filled Syringe. A total of 180 subjects will be randomized and will be stratified by weight group (55 to 69.9 kg, 70 to 84.9 kg and 85 to 100 kg). Within each of the 3 weight groups, subjects will be randomized 1:1:1:1:1:1 to 1 of the 6 combinations of treatment (APFS) with injection site (upper arm, abdomen or thigh)
干预措施: Benralizumab (Biological)
结局指标
主要结局
Area Under the Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast)
时间窗: At Pre-dose (Day 1) and at Days 2, 4, 5, 6, 8, 15, 29, 43 and 57
To compare the AUClast following single SC administration of Benralizumab by using APFS or AI devices
Maximum Observed Concentration (Cmax)
时间窗: At Pre-dose (Day 1) and at Days 2, 4, 5, 6, 8, 15, 29, 43 and 57
To compare the Cmax following single SC administration of Benralizumab by using APFS or AI devices
Area Under the Concentration-time Curve From Zero to Infinity (AUCinf)
时间窗: At Pre-dose (Day 1) and at Days 2, 4, 5, 6, 8, 15, 29, 43 and 57
To compare the AUCinf following single SC administration of Benralizumab by using APFS or AI devices
次要结局
- Time When Maximum Concentration is Observed (Tmax)(At Pre-dose (Day 1) and at Days 2, 4, 5, 6, 8, 15, 29, 43 and 57)
- Antidrug Antibody (ADA) Status(At predose (Day 1), Days 29 and 57)
- Terminal Half-life (t½)(At Pre-dose (Day 1) and at Days 2, 4, 5, 6, 8, 15, 29, 43 and 57)
- Number of Participants With Adverse Events(At predose and 2 h postdose (Day 1), Days 2, 4, 5, 6, 8, 15, 29, 43 and 57)
- Apparent Extravascular Clearance (CL/F)(At Pre-dose (Day 1) and at Days 2, 4, 5, 6, 8, 15, 29, 43 and 57)
- Apparent Volume of Distribution Based on the Terminal Phase (Vz/F)(At Pre-dose (Day 1) and at Days 2, 4, 5, 6, 8, 15, 29, 43 and 57)