A Study to Compare the Pharmacokinetics of Mepolizumab as a Liquid Drug in a Safety Syringe or an Autoinjector Versus Lyophilised Drug
2019年11月19日 更新者:GlaxoSmithKline
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
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.
研究概览
地位
完全的
条件
研究类型
介入性
注册 (实际的)
246
阶段
- 第三阶段
扩展访问
不再可用
查看扩展访问记录。
联系人和位置
本节提供了进行研究的人员的详细联系信息,以及有关进行该研究的地点的信息。
参与标准
研究人员寻找符合特定描述的人,称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。
资格标准
适合学习的年龄
18年 及以上 (成人、年长者)
接受健康志愿者
是的
有资格学习的性别
全部
描述
Inclusion Criteria
- 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 exclusion criteria, 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 1.
- 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.
学习计划
本节提供研究计划的详细信息,包括研究的设计方式和研究的衡量标准。
研究是如何设计的?
设计细节
- 主要用途:治疗
- 分配:随机化
- 介入模型:并行分配
- 屏蔽:无(打开标签)
武器和干预
参与者组/臂 |
干预/治疗 |
|---|---|
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实验性的: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.
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Mepolizumab will be provided as a clear to opalescent, colorless to pale yellow sterile solution for SC injection, supplied in a single-use, prefilled autoinjector or safety syringe containing 100 mg/mL mepolizumab with sodium phosphate, citric acid, sucrose ethylenediaminetetraacetic acid and polysorbate 80.
Single use, disposable safety syringe with a retracting needle guard and locking system.
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实验性的: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.
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Mepolizumab will be provided as a clear to opalescent, colorless to pale yellow sterile solution for SC injection, supplied in a single-use, prefilled autoinjector or safety syringe containing 100 mg/mL mepolizumab with sodium phosphate, citric acid, sucrose ethylenediaminetetraacetic acid and polysorbate 80.
Single use, disposable autoinjector will be assembled with the prefilled syringe containing the drug product.
It will enable automatic delivery of the drug product under the power of a spring mechanism following activation of the device.
Start and end of injection clicks will inform the user of correct use.
A plastic needle will cover shield the needle before and after injection to minimize the potential for needle stick injuries.
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有源比较器:Lyophilised mepolizumab from vial
Subjects will receive a single dose of 100 mg reconstituted lyophilized mepolizumab manually administered subcutaneously according to randomization
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Mepolizumab will be provided as white, uniform, lyophilized cake in vials with unit dose strength of 100 mg/vial for reconstitution in 1.2 mL sterile water for injection (SWFI).
Following reconstitution it forms a clear to opalescent, colorless to pale yellow solution for SC injection.
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研究衡量的是什么?
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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Maximum Observed Plasma Concentration (Cmax) of Mepolizumab
大体时间: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
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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.
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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
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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
大体时间: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
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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).
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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
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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Time to Cmax (Tmax) and Last Time Point Where the Concentration is Above the Limit of Quantification (Tlast) of Mepolizumab
大体时间: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
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Blood samples were collected at indicated time points.
Tmax and tlast following a single dose administration of liquid mepolizumab using a safety syringe and an autoinjector were compared with lyophilized drug product.
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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
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Apparent Clearance (CL/F) of Mepolizumab
大体时间: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
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Blood samples were collected at indicated time points .
CL/F following a single dose administration of liquid mepolizumab using a safety syringe and an autoinjector were compared with lyophilized drug product.
Only those participants with data available were analyzed.
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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
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Apparent Volume of Distribution (Vd/F) of Mepolizumab
大体时间: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
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Blood samples were collected at indicated time points.
Vd/F following a single dose administration of liquid mepolizumab using a safety syringe and an autoinjector were compared with lyophilized drug product.
Only those participants with data available were analyzed.
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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
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Terminal Phase Elimination Rate Constant (Lambda z) of Mepolizumab
大体时间: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
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Blood samples were collected at indicated time points.
Lambda z following a single dose administration of liquid mepolizumab using a safety syringe and an autoinjector were compared with lyophilized drug product.
Only those participants with data available were analyzed.
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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
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Terminal Phase Half-life (t½) of Mepolizumab
大体时间: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
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Blood samples were collected at indicated time points for calculating t½.
t½ following a single dose administration of liquid mepolizumab using a safety syringe and an autoinjector were compared with lyophilized drug product.
Only those participants with data available were analyzed.
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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
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Percentage of AUC(0-inf) Obtained by Extrapolation (% AUCex) of Mepolizumab
大体时间: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
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Blood samples were collected at indicated time points.
Percentage AUCex following a single dose administration of liquid mepolizumab using a safety syringe and an autoinjector were compared with lyophilized drug product.
Only those participants with data available were analyzed.
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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
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Number of Participants With On-treatment Non-serious Adverse Events (AEs) and Serious AEs (SAEs)
大体时间:Up to 28 days post-dose
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An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment or events associated with liver injury and impaired liver function were categorized as SAE.
All Treated Subjects (Safety) comprised of all participants who received mepolizumab.
Participants with non-serious AEs (3 percentage threshold) and SAEs has been reported.
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Up to 28 days post-dose
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Number of Participants With On-treatment Systemic Reactions and Injection Site Reactions
大体时间:Up to 28 days post-dose
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Adverse events of special interest like local injection site reactions and systemic reactions like allergic Type I hypersensitivity were reported along with AEs and SAEs.
Participants with local injection site reaction and Allergic Type I hypersensitivity systemic reactions are reported here.
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Up to 28 days post-dose
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Number of Participants With Hematology Parameters Shifts From Baseline Relative to Normal Range
大体时间:Up to Day 85
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Hematology parameters included assessment of platelet count, erythrocytes, leukocytes, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), neutrophils, lymphocytes, monocytes, eosinophils, basophils, hemoglobin and hematocrit.
Participants were counted in the worst case category that their value changes to Low, Normal or High.
Participants whose value category was unchanged or whose value became normal, were recorded in the "To Normal or No Change" category.
The worst case post-Baseline values has been reported.
For basophils the "to low" category is not applicable (NA) as the lower limit of normal is zero for this parameter.
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Up to Day 85
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Number of Participants With Clinical Chemistry Parameters Shifts From Baseline Relative to Normal Range
大体时间:Up to Day 85
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Blood samples were collected to evaluate clinical chemistry parameters, which included assessment of creatinine, creatine kinase, glucose, protein, potassium, urea, sodium, calcium, alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), direct bilirubin (D.bili) and bilirubin, and albumin.
Participants were counted in the worst case category that their value changes to Low, Normal or High.
Participants whose value category was unchanged or whose value became normal, were recorded in the "To Normal or No Change" category.
The worst case post-Baseline values has been reported.
Only those participants with data available at the specified data points were analyzed.
For the category "to low " NA indicates data was not available as the lower limit of normal is zero for this parameter.
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Up to Day 85
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Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)
大体时间:Baseline and up to Day 85
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SBP and DBP were measured in supine position after 5 minutes rest.
Baseline values for each assessment was the latest available assessment prior to receiving the single dose of mepolizumab.
Change from Baseline was defined as difference between the post-Baseline visit value and the Baseline value.
Only those participants available at the specified time points (represented by n=X in the category titles) were analyzed.
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Baseline and up to Day 85
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Change From Baseline in Pulse Rate
大体时间:Baseline and up to Day 85
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Pulse rate was measured in supine position after 5 minutes rest.
Baseline values for each assessment was the latest available assessment prior to receiving the single dose of mepolizumab.
Change from Baseline was defined as difference between the post-Baseline visit value and the Baseline value.
Only those participants available at the specified time points (represented by n=X in the category titles) were analyzed.
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Baseline and up to Day 85
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Change From Baseline in Temperature
大体时间:Baseline and up to Day 85
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Temperature was measured in supine position after 5 minutes rest.
Baseline values for each assessment was the latest available assessment prior to receiving the single dose of mepolizumab.
Change from Baseline was defined as difference between the post-Baseline visit value and the Baseline value.
Only those participants available at the specified time points (represented by n=X in the category titles) were analyzed.
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Baseline and up to Day 85
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Change From Baseline in Respiratory Rate
大体时间:Baseline and up to Day 85
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Respiratory rate was measured in supine position after 5 minutes rest.
Baseline values for each assessment was the latest available assessment prior to receiving the single dose of mepolizumab.
Change from Baseline was defined as difference between the post-Baseline visit value and the Baseline value.
Only those participants available at the specified time points (represented by n=X in the category titles) were analyzed.
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Baseline and up to Day 85
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Number of Participants With Change From Baseline in Electrocardiogram (ECG) Findings
大体时间:Baseline and Day 85
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Single measurements of 12-lead ECGs were obtained after 5 minutes of rest in a supine position for the participant.
ECG was performed on Day 1 and Day 85 using an automated ECG machine.
Baseline values for each assessment was the latest available assessment prior to receiving the single dose of mepolizumab.
Change from Baseline was defined as difference between the post-Baseline visit value and the Baseline value.
Participants with abnormal ECG findings that are clinically not significant and clinically significant data has been presented here.
The data of worst case post-Baseline is presented here.
Only those participants available at the specified time points were analyzed.
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Baseline and Day 85
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Number of Participants With Positive Anti-mepolizumab Binding Antibodies
大体时间:Up to Day 85
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Blood samples were collected for the determination of anti-mepolizumab antibodies.
A binding anti-drug antibody (ADA) assay was performed.
There were three tiered analysis: screening, confirmation and titration.
The results of binding ADA were categorized as negative, transient positive (defined as a single confirmatory positive immunogenic response that does not occur at the final study assessment) or persistent positive (defined as a confirmatory positive immunogenic response for at least 2 consecutive assessments excluding the Screening visit, or a single result at the final study assessment).
A participant was considered positive if they had at least one positive post-Baseline ADA result.
Number of participants with positive anti-mepolizumab antibodies at any time post-Baseline are presented here.
Only those participants available at the specified time points were analyzed.
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Up to Day 85
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Number of Participants With Positive Neutralizing Antibodies
大体时间:Up to Day 85
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Blood samples were collected for the determination of positive neutralizing antibodies.
A neutralizing antibody assay was performed.
Neutralizing antibody test was only carried out for participants who have had a positive confirmatory binding antibody test result at visit.
A participant was considered positive if they had at least one positive post-Baseline neutralizing antibody result.
Number of participants with positive neutralizing antibodies at any time post-Baseline are presented here.
Only those participants available at the specified time points were analyzed.
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Up to Day 85
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合作者和调查者
在这里您可以找到参与这项研究的人员和组织。
出版物和有用的链接
负责输入研究信息的人员自愿提供这些出版物。这些可能与研究有关。
研究记录日期
这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查,以确保它们在发布到公共网站之前符合特定的质量控制标准。
研究主要日期
学习开始 (实际的)
2017年1月6日
初级完成 (实际的)
2017年8月11日
研究完成 (实际的)
2017年8月11日
研究注册日期
首次提交
2016年12月15日
首先提交符合 QC 标准的
2017年1月6日
首次发布 (估计)
2017年1月9日
研究记录更新
最后更新发布 (实际的)
2019年12月3日
上次提交的符合 QC 标准的更新
2019年11月19日
最后验证
2019年11月1日
更多信息
与本研究相关的术语
其他研究编号
- 204958
- 2016-002405-19 (EudraCT编号)
计划个人参与者数据 (IPD)
计划共享个人参与者数据 (IPD)?
是的
IPD 计划说明
IPD for this study will be made available via the Clinical Study Data Request site.
IPD 共享时间框架
IPD is available via the Clinical Study Data Request site (click on the link provided below)
IPD 共享访问标准
Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place.
Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
IPD 共享支持信息类型
- 研究方案
- 树液
- 国际碳纤维联合会
- 企业社会责任
药物和器械信息、研究文件
研究美国 FDA 监管的药品
是的
研究美国 FDA 监管的设备产品
不
此信息直接从 clinicaltrials.gov 网站检索,没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求,请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改,我们的网站上也会自动更新.
Liquid mepolizumab的临床试验
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Istituti Clinici Scientifici Maugeri SpAUniversity of Palermo; National Research Council完全的
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GlaxoSmithKline不再可用
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Azienda Ospedaliero Universitaria di Cagliari邀请报名
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Sheffield Teaching Hospitals NHS Foundation TrustUniversity of Sheffield完全的
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Institut für Klinische Krebsforschung IKF GmbH...Roche Pharma AG完全的