To Evaluate Plasma and Pulmonary Pharmacokinetics of GSK2140944
2017年5月12日 更新者:GlaxoSmithKline
An Open-label Study To Evaluate Plasma and Pulmonary Pharmacokinetics Following Intravenous Administration of GSK2140944 in Healthy Adult Subjects (BTZ116666)
Antimicrobial penetration can be assessed through evaluation of antimicrobial concentrations in various lung compartments, including bronchial mucosal tissue, epithelial lining fluid (ELF), and alveolar macrophages (AM).
Antimicrobial concentrations determined in ELF and alveolar macrophages represent an ideal estimate of concentrations at the site of infection and can be accessed via bronchoalveolar lavage (BAL).
However sampling of antimicrobial concentrations via BAL is not routine in clinical practice due to its complex methodology and poor patient tolerability.
This study will evaluate intrapulmonary and plasma pharmacokinetics of GSK2140944 after single IV dose in adult healthy volunteers.
This is a Phase I, open-label study to evaluate plasma and pulmonary pharmacokinetics following intravenous administration of GSK2140944 in healthy adult participants.
Part A will evaluate the single dose PK profiles.
Part B is optional and will only be conducted if necessary.
Each part will consist of a maximum of 6 cohorts.
In Part A, only 4 of the 6 cohorts will be dosed initially; cohorts 5 and 6 are optional and will only be dosed if additional time-points are necessary to adequately model the pulmonary pharmacokinetic profile.
研究概览
研究类型
介入性
注册 (实际的)
22
阶段
- 阶段1
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。
学习地点
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Maryland
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Baltimore、Maryland、美国、21225
- GSK Investigational Site
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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 至 55年 (成人)
接受健康志愿者
不
有资格学习的性别
全部
描述
Inclusion Criteria:
- Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), alkaline phosphatase and bilirubin <=1.5x Upper limit of normal (ULN) (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
- Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, vital signs, electrocardiograms (ECGs), physical examination, and laboratory tests. A participant with a clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included if in the Investigator's judgement the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
- Male or female between 18 and 55 years of age inclusive, at the time of signing the informed consent. A female participant is eligible to participate if she is of non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea. To confirm post-menopausal status, a blood sample for simultaneous follicle stimulating hormone (FSH) > 40 milli-international units per milliliter (MlU/ml) and estradiol < 40 picrograms (pg)/ml (<147 picromoles/Liter [pmol/L]) is confirmatory. Male participant with female partners of child-bearing potential must agree to use one of the contraception methods listed as per protocol. This criterion must be followed from the time of the first dose of study medication until the final follow-up visit.
- Body weight >= 50 kg and Body mass index (BMI) within the range 19 - 31Kilograms/meter^2(kg/m^2) (inclusive).
- Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
Exclusion Criteria:
- Contraindications to bronchoalveolar lavage including hypercapnia >50 millimeters of mercury (mm Hg), known or suspected intolerability to medications necessary for bronchoscopy, refractory hypoxemia, reactive airway disease or asthma, unstable angina or acute myocardial infarction in the last 6 months, heart failure, and severe hemostatic alterations.
- A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening or positive Human Immunodeficiency Virus (HIV) antibody.
- Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
- Any clinically significant central nervous system (e.g., seizures), cardiac, pulmonary, metabolic, renal, hepatic or gastrointestinal conditions or history of such conditions that, in the opinion of the investigator may place the participant at an unacceptable risk as a participant in this trial or may interfere with the absorption, distribution, metabolism or excretion of drugs.
- A positive urine test for drugs of abuse or alcohol (or alcohol breath test) at screening.
- A screening urinalysis positive for protein or glucose (greater than "trace" findings of protein or glucose).
- A serum creatinine value that is out of the normal range, or an increase of 0.2 milligrams/decilitre (mg/dL) (or 15.25 micromoles/Liters [µmol/L]) in serum creatinine value between screening and Day -1 visit.
- History of photosensitivity to quinolones.
- Unwillingness to commit to avoid excessive exposure to sunlight (or exposure whilst on a tanning bed) which would cause a sunburn reaction from first dose up to and including the follow-up visit.
- History of drug abuse within 6 months of the study or a history of smoking or use of nicotine containing products within 3 months of screening, or a positive urine cotinine indicative of smoking at screening.
- History of regular alcohol consumption within 6 months of the study defined as: An average weekly intake of >14 drinks for males or >7 drinks for females. One drink is equivalent to 12 grams (g) of alcohol: 12 ounces (360 ml) of beer, 5 ounces (150 ml) of wine or 1.5 ounces (45 ml) of 80 proof distilled spirits.
- The participant has participated in a clinical trial and has received a drug or a new chemical entity within 30 days or 5 half-lives, or twice the duration of the biological effect of any drug (whichever is longer) prior to the first dose of current study medication.
- Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements within 7 days or 5 half-lives (whichever is longer) prior to the first dose of study medication, or use of St. John's Wort within 14 days prior to the first dose of study medication. By exception, the volunteer may take paracetamol or acetaminophen (<=2 grams/day) up to 48 hours prior to the first dose of study medication. However, the Investigator and GSK study team can review medication on a case by case basis to determine if its use would compromise participant safety or interfere with the study procedures or data interpretation.
- History of sensitivity to any of the study medications, including GSK2140944 and those that may be used in association with the BAL procedure, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation.
- Donation of blood in excess of 500 mL within 12 weeks prior to dosing.
- History of tendon rupture.
- History of sensitivity to heparin or heparin-induced thrombocytopenia (if the clinical research unit uses heparin to maintain intravenous cannula patency).
- Consumption of red wine, pomegranate, seville oranges, grapefruit or grapefruit juice, pummelos, exotic citrus fruits, grapefruit hybrids or fruit juices containing such products from 7 days prior to the first dose of study medication.
- Exclusion criteria for screening ECG (a single repeat is allowed for eligibility determination): Heart Rate, Males <40 and >100 Beat Per Minute (bpm), females <50 and >100 bpm; PR interval <120 and >220 msec; QRS duration <70 and >100 msec; A QT interval corrected for heart rate using the Bazett's formula (QTcB) or Single QT duration corrected for heart rate by Fridericia's formula (QTcF) interval >450 msec. Evidence of previous myocardial infarction (does not include ST segment changes associated with repolarization). A participant has Bundle Branch Block. Any conduction abnormality (including but not specific to left or right complete bundle branch block, AV block [2nd degree or higher], Wolf Parkinson White [WPW] syndrome), sinus pauses>3 seconds, non-sustained or sustained ventricular tachycardia (>=3 consecutive ventricular ectopic beats) or any significant arrhythmia which, in the opinion of the principal investigator and GSK medical monitor, will interfere with the safety of the individual participant.
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:非随机化
- 介入模型:单组作业
- 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:Part A(Cohort1)
Study BTZ116666 has two parts.
Each part will consist of a maximum of 6 cohorts.
Part A will be initiated with 4 initial cohorts/timepoints in order to minimize the number of healthy volunteers that undergo bronchoscopy in this study.
After review of data from Cohorts 1 through 4 of Part A, the study team will determine if additional cohorts are needed to be studied in Part A and/ or if Part B is needed.
If the study team determines that additional cohorts are needed, then only the necessary cohorts in Parts A and/or B will be executed.
In Part A, participants will receive GSK2140944 1000 mg intravenous (IV) infusion over 2 hours x 1 dose
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A lyophilized formulation, pale yellow to grayish yellow cake containing 750 mg of GSK2140944 (as free base) per vial, Administered intravenously as a single dose.
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实验性的:Part A (Cohort2)
In Part A, participants will receive GSK2140944 1000 mg intravenous (IV) infusion over 4 hours x 1 dose
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A lyophilized formulation, pale yellow to grayish yellow cake containing 750 mg of GSK2140944 (as free base) per vial, Administered intravenously as a single dose.
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实验性的:Part A (Cohort3)
In Part A, participants will receive GSK2140944 1000 mg intravenous (IV) infusion over 8 hours x 1 dose
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A lyophilized formulation, pale yellow to grayish yellow cake containing 750 mg of GSK2140944 (as free base) per vial, Administered intravenously as a single dose.
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实验性的:Part A (Cohort4)
In Part A, participants will receive GSK2140944 1000 mg intravenous (IV) infusion over 12 hours x 1 dose
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A lyophilized formulation, pale yellow to grayish yellow cake containing 750 mg of GSK2140944 (as free base) per vial, Administered intravenously as a single dose.
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实验性的:Part A (Cohort5)
In Part A, participants will receive GSK2140944 1000 mg intravenous (IV) infusion.
Optional Cohort or Part and will only be used if necessary.
Sampling times are to be determined based on the review of preliminary PK results from prior study parts and/or cohorts.
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A lyophilized formulation, pale yellow to grayish yellow cake containing 750 mg of GSK2140944 (as free base) per vial, Administered intravenously as a single dose.
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实验性的:Part A (Cohort6)
In Part A, participants will receive GSK2140944 1000 mg intravenous (IV) infusion.
Optional Cohort or Part and will only be used if necessary.
Sampling times are to be determined based on the review of preliminary PK results from prior study parts and/or cohorts.
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A lyophilized formulation, pale yellow to grayish yellow cake containing 750 mg of GSK2140944 (as free base) per vial, Administered intravenously as a single dose.
|
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实验性的:Part B (Cohort1)
In Part B, participants will receive GSK2140944 1000 mg IV infusion, q12h x 5 doses.
Optional Cohort or Part and will only be used if necessary.
Sampling times are to be determined based on the review of preliminary PK results from prior study parts and/or cohorts.
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A lyophilized formulation, pale yellow to grayish yellow cake containing 750 mg of GSK2140944 (as free base) per vial, Administered intravenously every 12 hours for 5 doses (3 days).
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实验性的:Part B (Cohort2)
In Part B, participants will receive GSK2140944 1000 mg IV infusion over, q12h x 5 doses.
Optional Cohort or Part and will only be used if necessary.
Sampling times are to be determined based on the review of preliminary PK results from prior study parts and/or cohorts.
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A lyophilized formulation, pale yellow to grayish yellow cake containing 750 mg of GSK2140944 (as free base) per vial, Administered intravenously every 12 hours for 5 doses (3 days).
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实验性的:Part B (Cohort3)
In Part B, participants will receive GSK2140944 1000 mg IV infusion over, q12h x 5 doses.
Optional Cohort or Part and will only be used if necessary.
Sampling times are to be determined based on the review of preliminary PK results from prior study parts and/or cohorts.
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A lyophilized formulation, pale yellow to grayish yellow cake containing 750 mg of GSK2140944 (as free base) per vial, Administered intravenously every 12 hours for 5 doses (3 days).
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实验性的:Part B (Cohort4)
In Part B, participants will receive GSK2140944 1000 mg IV infusion over q12h x 5 doses.
Optional Cohort or Part and will only be used if necessary.
Sampling times are to be determined based on the review of preliminary PK results from prior study parts and/or cohorts.
|
A lyophilized formulation, pale yellow to grayish yellow cake containing 750 mg of GSK2140944 (as free base) per vial, Administered intravenously every 12 hours for 5 doses (3 days).
|
|
实验性的:Part B (Cohort5)
In Part B, participants will receive GSK2140944 1000 mg IV infusion over, q12h x 5 doses.
Optional Cohort or Part and will only be used if necessary.
Sampling times are to be determined based on the review of preliminary PK results from prior study parts and/or cohorts.
|
A lyophilized formulation, pale yellow to grayish yellow cake containing 750 mg of GSK2140944 (as free base) per vial, Administered intravenously every 12 hours for 5 doses (3 days).
|
|
实验性的:Part B (Cohort6)
In Part B, participants will receive GSK2140944 1000 mg IV infusion over, q12h x 5 doses.
Optional Cohort or Part and will only be used if necessary.
Sampling times are to be determined based on the review of preliminary PK results from prior study parts and/or cohorts.
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A lyophilized formulation, pale yellow to grayish yellow cake containing 750 mg of GSK2140944 (as free base) per vial, Administered intravenously every 12 hours for 5 doses (3 days).
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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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Pulmonary pharmacokinetics of GSK2140944 following intravenous single-dose administration.
大体时间:Day 1, Day 2, Day 3
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Blood samples will be collected assessment of PK parameters including Epithelial Lining Fluid (ELF) and Alveolar Macrophages (AM) (AUC[0- τ]), Area under the concentration-time curve from time zero (pre-dose) to last time of quantifiable concentration within a participant across all treatments (AUC[0-t]), Maximum observed concentration (Cmax), Time of occurrence of Cmax (tmax), ELF and AM/plasma ratios for GSK2140944 at the early, mid and late dosing interval timepoints, and AUCELF/AUC plasma and AUCAM/AUC plasma ratios, as data permit.
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Day 1, Day 2, Day 3
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Plasma pharmacokinetics of GSK2140944 following intravenous single-dose administration.
大体时间:Day 1, Day 2, Day 3
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Blood sample will be collected for estimation of relative bioavailability and assessment of PK parameters including maximum observed concentration; Cmax, area under the concentration-time curve from time 0 to time t; AUC (0-t) and area under the concentration-time curve from time 0 to infinity; AUC(0-infinity), Systemic clearance of parent drug (CL), Volume of distribution at steady state of parent drug after intravascular (e.g., IV) administration (Vdss) and Terminal phase half-life (t½).
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Day 1, Day 2, Day 3
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Pulmonary pharmacokinetics of GSK2140944 following repeat daily multiple intravenous dose administration.
大体时间:Day1, Day 2, Day 3, Day 4, Day 5
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Blood samples will be collected assessment of PK parameters including ELF and AM AUC(0- τ)), AUC(0-t), Cmax, tmax, ELF and AM/plasma ratios for GSK2140944 at the early, mid and late dosing interval timepoints, and AUCELF/AUC plasma and AUCAM/AUC plasma ratios, as data permit.
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Day1, Day 2, Day 3, Day 4, Day 5
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Plasma pharmacokinetics of GSK2140944 following repeat daily multiple intravenous dose administration.
大体时间:Day1, Day 2, Day 3, Day 4, Day 5
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Blood sample will be collected for estimation of relative bioavailability and assessment of PK parameters including maximum observed concentration; Cmax, area under the concentration-time curve from time 0 to time t; AUC (0-t) and area under the concentration-time curve from time 0 to infinity; AUC(0-infinity), Systemic clearance of parent drug (CL), Volume of distribution at steady state of parent drug after intravascular (e.g., IV) administration (Vdss) and Terminal phase half-life (t½).
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Day1, Day 2, Day 3, Day 4, Day 5
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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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Characterisation of the safety profile of GSK2140944 with adverse events (AEs) following intravenous single-dose administration
大体时间:Up to study day 15
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AE is defined as Any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
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Up to study day 15
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Characterisation of the safety profile of GSK2140944 with chemistry and haematology laboratory values following intravenous single-dose administration
大体时间:Up to study day 15
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Any abnormal laboratory test results (haematology, clinical chemistry, or urinalysis)
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Up to study day 15
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Characterisation of the safety profile of GSK140944 electrocardiograms (ECG) following intravenous single-dose administration
大体时间:Up to study day 15
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Twelve (12)-lead ECGs will be obtained using an ECG machine that automatically calculates heart rate and measures PR, QRS, QT, RR and QTcB intervals.
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Up to study day 15
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Characterisation of the safety profile of GSK2140944 with vital signs following intravenous single-dose administration
大体时间:Up to study day 15
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Vital sign measurements will include systolic and diastolic blood pressure, body temperature, pulse rate.
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Up to study day 15
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Characterisation of the safety profile of GSK2140944 with adverse events (AEs) following repeat daily multiple intravenous dose administration
大体时间:Up to study day 18
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AE is defined as Any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
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Up to study day 18
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Characterisation of the safety profile of GSK2140944 with chemistry and haematology laboratory values following repeat daily multiple intravenous dose administration
大体时间:Up to study day 18
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Any abnormal laboratory test results (haematology, clinical chemistry, or urinalysis)
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Up to study day 18
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Characterisation of the safety profile of GSK140944 electrocardiograms (ECG) following repeat daily multiple intravenous dose administration
大体时间:Up to study day 18
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Twelve (12)-lead ECGs will be obtained using an ECG machine that automatically calculates heart rate and measures PR, QRS, QT, RR and QTcB intervals.
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Up to study day 18
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Characterisation of the safety profile of GSK2140944 with vital signs following repeat daily multiple intravenous dose administration
大体时间:Up to study day 18
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Vital sign measurements will include systolic and diastolic blood pressure, body temperature, pulse rate.
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Up to study day 18
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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)
2013年9月25日
初级完成 (实际的)
2013年12月21日
研究完成 (实际的)
2013年12月21日
研究注册日期
首次提交
2013年8月29日
首先提交符合 QC 标准的
2013年8月29日
首次发布 (估计)
2013年9月4日
研究记录更新
最后更新发布 (实际的)
2017年5月15日
上次提交的符合 QC 标准的更新
2017年5月12日
最后验证
2017年5月1日
更多信息
与本研究相关的术语
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
Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
研究数据/文件
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带注释的病例报告表
信息标识符:116666信息评论:For additional information about this study please refer to the GSK Clinical Study Register
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个人参与者数据集
信息标识符:116666信息评论:For additional information about this study please refer to the GSK Clinical Study Register
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临床研究报告
信息标识符:116666信息评论:For additional information about this study please refer to the GSK Clinical Study Register
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知情同意书
信息标识符:116666信息评论:For additional information about this study please refer to the GSK Clinical Study Register
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数据集规范
信息标识符:116666信息评论:For additional information about this study please refer to the GSK Clinical Study Register
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统计分析计划
信息标识符:116666信息评论:For additional information about this study please refer to the GSK Clinical Study Register
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研究协议
信息标识符:116666信息评论:For additional information about this study please refer to the GSK Clinical Study Register
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.