A Randomized, Parallel-Group, Open-Label Study to Evaluate the Absolute Bioavailability, Pharmacokinetics, Tolerability and Safety of a High Concentration Formulation of Belimumab (HGS1006), a Fully Human Monoclonal Anti-BLyS Antibody, Administered Subcutaneously to Healthy Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 118
- 试验地点
- 4
- 主要终点
- Time to Reach Maximum Serum Drug Concentration (Tmax) Following a Single Dose of Belimumab Given as Intravenous Infusion (IV) or Subcutaneous Injection (SC)
研究概览
简要总结
The purpose of this study is to measure the amount of belimumab in the blood when given as an injection under the skin (subcutaneously; SC) and to evaluate the safety and tolerability of multiple injections under the skin in healthy subjects.
详细描述
This study is designed to evaluate the absolute bioavailability, pharmacokinetics, tolerability, and safety of a single dose (groups 1-4) or multiple doses (groups 5-6) of belimumab administered subcutaneously (SC) to healthy subjects.
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 subjects defined as no clinically relevant abnormalities identified by a detailed medical history, full physical exam, 12-lead electrocardiogram (ECG), and clinical laboratory tests.
- •Body weight between 45 to 120 kg (99 to 264 lbs).
- •Must agree to use effective contraception throughout the study and for 14 weeks after administration of belimumab.
- •Have the ability to understand the requirements of the study, provide written informed consent, and comply with the study protocol procedures.
排除标准
- •Pregnant or nursing.
- •Test positive for drugs or alcohol or have had a drug or alcohol dependence within the past year.
- •Have used any prescription medicines within the past 30 days or herbal/botanical supplements within the past 7 days or anticipate use during the study. May use prescription contraceptives, hormone replacement therapy, and over-the-counter medicines such as antihistamines or nutritional support such as vitamins, minerals, or amino acids.
- •Have received a live vaccine within the past 30 days or anticipate receipt of a live vaccine during the study and within 4 months after last injection of belimumab.
- •Have a history of an allergic or anaphylactic reaction to drugs, food, or insect bite or sting requiring medical intervention.
- •Have a history of allergic reaction to contrast agents or biological medicines.
- •Have participated in a clinical trial and received an experimental medicine within the past 60 days.
- •Have received treatment with a B cell targeted therapy at any time.
- •Have required management of an infection within the past 14 days.
研究组 & 干预措施
Belimumab SC 1 x 200 mg weekly
干预措施: Multiple Dose Group: Belimumab SC 1 x 200 mg weekly (Biological)
Belimumab IV 240 mg
干预措施: Single Dose Group: Belimumab IV 240 mg (Biological)
Belimumab SC 2 x 120 mg weekly
干预措施: Multiple Dose Group: Belimumab SC 2 x 120 mg weekly (Biological)
Belimumab SC 2 x 120 mg
干预措施: Single Dose Group: Belimumab SC 2 x 120 mg (Biological)
Belimumab SC 1 x 240 mg
干预措施: Single Dose Group: Belimumab SC 1 x 240 mg (Biological)
Belimumab SC 1 x 200 mg
干预措施: Single Dose Group: Belimumab SC 1 x 200 mg (Biological)
结局指标
主要结局
Time to Reach Maximum Serum Drug Concentration (Tmax) Following a Single Dose of Belimumab Given as Intravenous Infusion (IV) or Subcutaneous Injection (SC)
时间窗: Pre-dose, Post-dose on Days 0, 1, 2, 3, 4, 5, 6, 7, 10, 14, 21, 28, 42, 56, and 70
Area Under the Serum Drug Concentration-time Curve From Time 0 to Infinite Time (AUC0-∞) Following a Single Dose of Belimumab Given as IV or SC
时间窗: Pre-dose, Post-dose on Days 0, 1, 2, 3, 4, 5, 6, 7, 10, 14, 21, 28, 42, 56, and 70
AUC (0-∞) = Area under the serum drug concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-∞). It is obtained from AUC (0-last) plus C (last)/λz. C (last) is the last measurable concentration. λz was determined by linear regression (r2 ≥ 0.8) with uniform weighting of all data in the terminal linear portion of the log-transformed drug concentration-time profile.
Maximum Serum Drug Concentration (Cmax) Following a Single Dose of Belimumab Given as IV or SC
时间窗: Pre-dose, Post-dose on Days 0, 1, 2, 3, 4, 5, 6, 7, 10, 14, 21, 28, 42, 56, and 70
Terminal Elimination Half-life (t1/2,Term) Following a Single Dose of Belimumab Given as IV or SC
时间窗: Pre-dose, Post-dose on Days 0, 1, 2, 3, 4, 5, 6, 7, 10, 14, 21, 28, 42, 56, and 70
Terminal elimination half-life is the time measured for the serum drug concentration of belimumab to decrease by one half.
Absolute Bioavailability of a Single Dose of Belimumab Given as IV or SC
时间窗: Pre-dose, Post-dose on Days 0, 1, 2, 3, 4, 5, 6, 7, 10, 14, 21, 28, 42, 56, and 70
Bioavailability (F) is a measurement of the rate and extent to which a drug reaches the systemic circulation. The bioavailability of belimumab administered by IV is compared to the bioavailability of belimumab administered via single-SC injection.
次要结局
- Area Under the Serum Drug Concentration-time Curve From Time 0 to Infinite Time (AUC0-∞) Following Weekly (x 4) SC Injections of Belimumab(Pre-dose, Post-dose on Days 0, 1, 2, 3, 4, 5, 6, 7, 14, 21, 22, 23, 24, 25, 26, 27, 28, 31, 35, 42, 49, 63, 77, 91, and 119)
- Time to Reach Maximum Serum Drug Concentration (Tmax) Following Weekly (x 4) SC Injections of Belimumab(Pre-dose, Post-dose on Days 0, 1, 2, 3, 4, 5, 6, 7, 14, 21, 22, 23, 24, 25, 26, 27, 28, 31, 35, 42, 49, 63, 77, 91, and 119)
- Maximum Serum Drug Concentration (Cmax) Following Weekly (x 4) SC Injections of Belimumab(Pre-dose, Post-dose on Days 0, 1, 2, 3, 4, 5, 6, 7, 14, 21, 22, 23, 24, 25, 26, 27, 28, 31, 35, 42, 49, 63, 77, 91, and 119)
- Terminal Elimination Half-life (t1/2,Term) Following Weekly (x 4) SC Injections of Belimumab(Pre-dose, Post-dose on Days 0, 1, 2, 3, 4, 5, 6, 7, 14, 21, 22, 23, 24, 25, 26, 27, 28, 31, 35, 42, 49, 63, 77, 91, and 119)
- Absolute Bioavailability of Weekly (x 4) SC Injections of Belimumab(Pre-dose, Post-dose on Days 0, 1, 2, 3, 4, 5, 6, 7, 14, 21, 22, 23, 24, 25, 26, 27, 28, 31, 35, 42, 49, 63, 77, 91, and 119)
- Number of Participants Who Experienced Adverse Events(Up to Day 119)