An Open Label, Randomised, Three Arm, Single Dose, Multicentre, Parallel Group Study in Healthy Subjects to Compare the Pharmacokinetics of Subcutaneous Mepolizumab When Delivered as a Liquid Drug Product in a Safety Syringe or an Auto Injector With a Reconstituted Lyophilised Drug Product From a Vial
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 246
- 试验地点
- 3
- 主要终点
- Area Under the Plasma Concentration Time Curve (AUC) From Time Zero to the Time of Last Quantifiable Concentration (AUC[0-t]), AUC From Time Zero Extrapolated to Infinite Time (AUC[0-inf]) of Mepolizumab
研究概览
简要总结
Mepolizumab (SB-240563) is a humanized monoclonal antibody (Immunoglobulin G1, kappa, mAb) that blocks human interleukin-5 (hIL-5) from binding to the interleukin (IL)-5 receptor complex expressed on the eosinophil cell surface and thus inhibits signaling. This study will compare the pharmacokinetics and safety of mepolizumab administered as a liquid drug product in two different devices with the reconstituted lyophilized drug product in healthy subjects. Subjects will receive a single administration of 100 milligram (mg) mepolizumab as a single injection. The randomization will be stratified by body weight (<70 kilogram (kg), 70 <80 kg and >=80 kg) and the site of injection will be randomized 1:1:1 to the upper arm, abdomen or thigh. Approximately 243 healthy subjects will be randomized so that at least 9 subjects are randomized to each mepolizumab treatment within each weight strata and 3 subjects within each mepolizumab treatment, weight strata and injection site. Each subject will participate in the study for up to approximately 16 weeks (up to 85 days after drug administration), and will have a screening visit, a single dose treatment period, and a follow-up visit.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •18 years of age and over at the time of signing the informed consent.
- •Healthy as determined by the investigator or medically qualified designee based on a medical evaluation including medical history, physical examination, vital signs, laboratory tests, and cardiac monitoring. A subject with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or
排除标准
- •, outside the reference range for the population being studied may be included only if the investigator agrees and documents that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures or ability to interpret study results.
- •Body weight >=50 kg and body mass index (BMI) within the range 19.0-30 kg/square meter(m^2) (inclusive)
- •Male or Female: A female subject is eligible to participate if she is not pregnant (as confirmed by a negative human chorionic gonadotrophin (hCG) test), not lactating, and at least one of the following conditions applies: Non-reproductive potential defined as: pre-menopausal females with documented tubal ligation; documented hysteroscopic tubal occlusion procedure with follow-up; confirmation of bilateral tubal occlusion; hysterectomy; documented bilateral oophorectomy; post- menopausal females. Subject is of reproductive potential and agrees to follow one of the options listed in the Modified List of Highly Effective Methods for Avoiding Pregnancy in Females of Reproductive Potential (FRP) from 30 days prior to the first dose of study medication and until 16 weeks after the administration of the single dose of study medication.
- •Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the consent form and in the protocol. The subject must be able to understand and communicate in the native language of the site, e.g. German in German sites.
- •Exclusion Criteria
- •Alanine transaminase >1.5x upper limit of normal (ULN)
- •Bilirubin >1.5xULN (isolated bilirubin >1.5x ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
- •Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)
- •QTc corrected by Fridericia's (QTcF) formula>450 milliseconds (msec)
- •Any clinically relevant abnormality identified at the screening medical assessment (physical examination/medical history), clinical laboratory tests, or 12-lead electrocardiogram.
- •Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half lives (whichever is longer) before the first dose of study medication and until study completion, unless in the opinion of the investigator and GlaxoSmithKline Medical Monitor the medication will not interfere with the study procedures or compromise subject safety.
- •History of regular alcohol consumption within 6 months of the study defined as: an average weekly intake of >14 units for females and >21 units for males. One unit is equivalent to 8 grams of alcohol: a half-pint (~240 milliliter [mL]) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.
- •Urinary nicotine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products within 6 months prior to screening. Limit of >500 nanogram/mL.
- •Involved in any activities likely to result in any significant decrease or increase in body weight during the study period (e.g. 'crash' dieting, bodybuilding).
- •History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or Medical Monitor, contraindicates their participation.
- •Presence of hepatitis B surface antigen (HBsAg), positive hepatitis C antibody test result at screening or within 3 months prior to first dose of study treatment.
- •A positive test for human immunodeficiency virus antibody.
- •Subjects with known, pre-existing helminthes infestation within 6 months prior to Day
- •Where participation in the study would result in donation of blood or blood products in excess of 500 mL within 3 months.
- •The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
- •Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
- •A positive pre-study drug/alcohol screen.
- •A vulnerable subject. Defined as individuals whose willingness to volunteer in a clinical trial may be unduly influenced by the expectation, whether justified or not, of benefits associated with participation, or of a retaliatory response from senior members of a hierarchy in case of refusal to participate.
- •Subjects who work for the Sponsor, contract research organization, or one of the study centers.
研究组 & 干预措施
Liquid mepolizumab in an autoinjector
Subjects will receive a single dose of 100 mg liquid mepolizumab administered subcutaneously using a prefilled autoinjector, according to randomization.
干预措施: Liquid mepolizumab (Biological)
Liquid mepolizumab in safety syringe
Subjects will receive a single dose of 100 mg liquid mepolizumab administered subcutaneously using a prefilled syringe within a safety syringe according to randomization.
干预措施: Liquid mepolizumab (Biological)
Liquid mepolizumab in safety syringe
Subjects will receive a single dose of 100 mg liquid mepolizumab administered subcutaneously using a prefilled syringe within a safety syringe according to randomization.
干预措施: Prefilled Safety Syringe (Device)
Liquid mepolizumab in an autoinjector
Subjects will receive a single dose of 100 mg liquid mepolizumab administered subcutaneously using a prefilled autoinjector, according to randomization.
干预措施: Prefilled autoinjector (Device)
Lyophilised mepolizumab from vial
Subjects will receive a single dose of 100 mg reconstituted lyophilized mepolizumab manually administered subcutaneously according to randomization
干预措施: Lyophilized mepolizumab (Biological)
结局指标
主要结局
Area Under the Plasma Concentration Time Curve (AUC) From Time Zero to the Time of Last Quantifiable Concentration (AUC[0-t]), AUC From Time Zero Extrapolated to Infinite Time (AUC[0-inf]) of Mepolizumab
时间窗: Day 1 (pre-dose, 2 hours, and 8 hours post-dose), Days 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 22, 29, 43, 57 and 85 post-dose
Blood samples were collected at indicated time points. AUC(0-t) and AUC(0-inf) following a single dose administration of liquid mepolizumab using a safety syringe and an autoinjector were compared with lyophilized drug product. Fixed effects analysis of covariance model was used for analysis. Only those participants with data available at the specified data points were analyzed (represented by n=X in category titles).
Maximum Observed Plasma Concentration (Cmax) of Mepolizumab
时间窗: Day 1 (pre-dose, 2 hours, and 8 hours post-dose), Days 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 22, 29, 43, 57 and 85 post-dose
Blood samples were collected at indicated time points. Cmax following a single dose administration of liquid mepolizumab using a safety syringe and an autoinjector were compared with reconstituted lyophilized drug product from the vial. Pharmacokinetic (PK) Population comprised of all participants receiving study drug for whom a pharmacokinetic sample was obtained and analyzed.
次要结局
- Apparent Clearance (CL/F) of Mepolizumab(Day 1 (pre-dose, 2 hours, and 8 hours post-dose), Days 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 22, 29, 43, 57 and 85 post-dose)
- Terminal Phase Elimination Rate Constant (Lambda z) of Mepolizumab(Day 1 (pre-dose, 2 hours, and 8 hours post-dose), Days 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 22, 29, 43, 57 and 85 post-dose)
- Terminal Phase Half-life (t½) of Mepolizumab(Day 1 (pre-dose, 2 hours, and 8 hours post-dose), Days 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 22, 29, 43, 57 and 85 post-dose)
- Apparent Volume of Distribution (Vd/F) of Mepolizumab(Day 1 (pre-dose, 2 hours, and 8 hours post-dose), Days 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 22, 29, 43, 57 and 85 post-dose)
- Time to Cmax (Tmax) and Last Time Point Where the Concentration is Above the Limit of Quantification (Tlast) of Mepolizumab(Day 1 (pre-dose, 2 hours, and 8 hours post-dose), Days 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 22, 29, 43, 57 and 85 post-dose)
- Percentage of AUC(0-inf) Obtained by Extrapolation (% AUCex) of Mepolizumab(Day 1 (pre-dose, 2 hours, and 8 hours post-dose), Days 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 22, 29, 43, 57 and 85 post-dose)
- Number of Participants With On-treatment Systemic Reactions and Injection Site Reactions(Up to 28 days post-dose)
- Number of Participants With Hematology Parameters Shifts From Baseline Relative to Normal Range(Up to Day 85)
- Number of Participants With On-treatment Non-serious Adverse Events (AEs) and Serious AEs (SAEs)(Up to 28 days post-dose)
- Number of Participants With Clinical Chemistry Parameters Shifts From Baseline Relative to Normal Range(Up to Day 85)
- Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)(Baseline and up to Day 85)
- Change From Baseline in Pulse Rate(Baseline and up to Day 85)
- Change From Baseline in Temperature(Baseline and up to Day 85)
- Change From Baseline in Respiratory Rate(Baseline and up to Day 85)
- Number of Participants With Change From Baseline in Electrocardiogram (ECG) Findings(Baseline and Day 85)
- Number of Participants With Positive Anti-mepolizumab Binding Antibodies(Up to Day 85)
- Number of Participants With Positive Neutralizing Antibodies(Up to Day 85)