First Time in Human Study With GSK1325756
A Single-centre, Double-blind, Placebo-controlled Study to Evaluate the Safety, Tolerabilty, Pharmacokinetics, and Pharmacodynamics of Single, Oral, Ascending Doses and Repeat Oral Doses of GSK1325756 in Healthy Male Subjects.
研究概览
详细说明
This study will evaluate the safety, tolerability, pharmacokinetics(PK) and pharmacodynamics (PD) of single and repeat oral doses of GSK1325756 in healthy, male volunteer subjects, including the assessment of the effect of GSK1325756 on ex vivo 'C-X-C Motif Ligand 1' (CXCL1)-induced 'Cluster of Differentiation 11b' (CD11b) cell surface expression on peripheral blood neutrophils. Selective antagonism of the interaction between 'C-X-C Receptor Type 2' (CXCR2) and its various chemokine ligands provides a potential strategy for reducing the underlying inflammation that contributes to the progression of Chronic Obstructive Pulmonary Disease (COPD). This study is the first administration of GSK1325756 to humans and will be conducted in four cohorts.
Cohorts 1 and 2 will comprise of a double-blind, placebo-controlled, single dose escalation of GSK132576 in healthy adult males in two interlocking cohorts.
The data generated from this single dose escalation component of the study (safety, tolerability, and where applicable, PK profile, and, if available, PD data) will enable decisions regarding progression from one to dose the next higher dose later within Cohorts 1 and 2. This data will also be reviewed in decisions regarding study progression to repeat dosing in Cohorts 3 and 4, and the most suitable doses of GSK1325756 that should be selected for these repeat dose cohorts.
研究类型
注册 (实际的)
阶段
- 阶段1
联系人和位置
学习地点
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London、英国、NW10 7EW
- GSK Investigational Site
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参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
Inclusion Criteria:
- Aspartate Transaminase (AST), Alanine Transaminase (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, physical examination, laboratory tests and Electrocardiogram (ECG). A subject with a clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included only if the Investigator and the GSK Medical Monitor agree that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
- Males between 18 and 65 years of age inclusive, at the time of signing the informed consent.
- Subjects must agree to use one of the contraception methods listed below:
To prevent pregnancy in a female partner or to prevent exposure of any partner to the investigational product from a male subject's semen, male subjects must use one of the following contraceptive methods:
- Abstinence, defined as sexual inactivity consistent with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.
- Condom (during non-vaginal intercourse with any partner - male or female) OR
Condom and occlusive cap (diaphragm or cervical/vault caps) plus spermicidal agent (foam/gel/film/cream/suppository) (during sexual intercourse with a female) This criterion must be followed from the time of the first dose of study medication until at least 3-months post-last dose of study drug.
- Body weight ≥ 60 kilograms (kg) and Body Mass Index (BMI) within the range 19 - 31 kilogrammes per square metre (kg/m-2) (inclusive)
- 12-lead ECG without any clinically significant abnormality as judged by the Investigator, and average QTcB or QTcF (ECG paramaters) < 450 msec
- Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
- Able to complete all study procedures and planned treatment periods.
Exclusion Criteria:
- Cotinine or Exhaled Breath Carbon Monoxide (CO) Test indicative of current smoking or history or regular use of tobacco- or nicotine-containing products within 6 months prior to screening.
- A neutrophil count at screening of < 2 x 10(9) per litre (/L)
- A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening
- Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
- Significant cardiac, pulmonary, metabolic, renal, gastrointestinal or other conditions that in the opinion of the investigator and/or GSK medical monitor, places the subject at an unacceptable risk as participant in this trial
- A positive pre-study drug/alcohol screen.
- A positive test for HIV antibody.
- History of regular alcohol consumption within 6 months of the study defined as an average weekly intake of >21 units for males. One unit is equivalent to 8 grams of alcohol: a half-pint (~240 milliLitres(mL)) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.
- 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: 3 months, 5 half-lives or twice the duration of the expected 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.
- 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) prior to the first dose of study medication, unless in the opinion of the Investigator and GSK Medical Monitor the medication will not interfere with the study procedures or compromise subject safety. Prescription and non-prescription non-steroidal anti-inflammatory drugs are not permitted.
- 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 GSK Medical Monitor, contraindicates their participation.
- Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.
- Subject is mentally or legally incapacitated.
- Consumption of red wine, seville oranges, grapefruit or grapefruit juice and/or pummelos, exotic citrus fruits, grapefruit hybrids or fruit juices from 7 days prior to the first dose of study medication.
学习计划
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:交叉作业
- 屏蔽:双倍的
武器和干预
参与者组/臂 |
干预/治疗 |
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实验性的:COHORT 1
Interlocking design with Cohort 2. Single dose; treatment period over 2 days such that two subjects will receive GSK1325756 and at least one subject will receive placebo on Day 1.
The remaining subjects will be dosed on day 2 of each treatment period assuming adequate safety from Day 1. Placebo and an escalation of GSK1325756 from 10mg, to 50mg, and 200mg, will be administered over the 6 week long treatment period allowing adequate washout period between doses.
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Drug will be orally administered in varying amounts over varying time periods as detailed in the 'arms' section.
Placebo will be orally administered to at least 4 subjects in each treatment period of each cohort.
In each sequence in each cohort, all subjects will receive one dose of placebo.
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实验性的:COHORT 2
Interlocking design with Cohort 1. Single dose; treatment period over 2 days such that two subjects will receive GSK1325756 and at least one subject will receive placebo on Day 1.
The remaining subjects will be dosed on day 2 of each treatment period assuming adequate safety from Day 1. Placebo and an escalation of GSK1325756 from 25mg, to 100mg, and 400mg, will be administered over the 6 week long treatment period allowing adequate washout period between doses.
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Drug will be orally administered in varying amounts over varying time periods as detailed in the 'arms' section.
Placebo will be orally administered to at least 4 subjects in each treatment period of each cohort.
In each sequence in each cohort, all subjects will receive one dose of placebo.
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实验性的:COHORT 3
Placebo controlled, 14-day, once daily, repeat-dose evaluation with one selected dose of GSK1325756 in 14 subjects.
Dose selection based on review of safety and tolerability data from cohorts 1 and 2.
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Drug will be orally administered in varying amounts over varying time periods as detailed in the 'arms' section.
Placebo will be orally administered to at least 4 subjects in each treatment period of each cohort.
In each sequence in each cohort, all subjects will receive one dose of placebo.
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实验性的:COHORT 4
Placebo controlled, 14-day, once daily, repeat-dose evaluation with a higher selected dose of GSK1325756 in 14 subjects.
Dose selection based on review of safety and tolerability data from cohort 3.
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Drug will be orally administered in varying amounts over varying time periods as detailed in the 'arms' section.
Placebo will be orally administered to at least 4 subjects in each treatment period of each cohort.
In each sequence in each cohort, all subjects will receive one dose of placebo.
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研究衡量的是什么?
主要结果指标
结果测量 |
大体时间 |
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Safety and tolerabilty of GSK1325756 as assessed by clinical monitoring of blood pressure, pulse rate, ECG, and laboratory data, as well as reporting of AEs.
大体时间:Study duration
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Study duration
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次要结果测量
结果测量 |
大体时间 |
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Area under the blood concentration-time curve, Maximum Concentration (Cmax), Time to Cmax (Tmax), terminal half-life and oral clearance of GSK1325756 following the administration of single escalating oral doses of GSK1325756 in healthy adult subjects.
大体时间:Study duration
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Study duration
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Area under the blood drug concentration-time curve, trough 24-hour Concentration (C24), Cmax, Tmax and accumulation of GSK1325756 following the administration of once daily repeat doses of two selected doses of GSK1325756 for 14 days in healthy subjects.
大体时间:Study duration
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Study duration
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Flow cytometric quantification of CXCL1-induced CD11b cell surface expression on peripheral blood neutrophils ex vivo following the administration of single and repeat oral doses of GSK1325756 in healthy adult subjects
大体时间:Study duration
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Study duration
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PK-PD model of the relationship between the blood concentration of GSK1325756 and CXCL1-induced CD11b cell surface expression on neutrophils ex vivo following the administration of single and repeat oral doses of GSK1325756 in healthy adult subjects
大体时间:Study duration
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Study duration
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合作者和调查者
出版物和有用的链接
研究记录日期
研究主要日期
学习开始 (实际的)
初级完成 (实际的)
研究完成 (实际的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (估计)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
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)?
IPD 计划说明
研究数据/文件
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数据集规范
信息标识符:112483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:112483信息评论:For additional information about this study please refer to the GSK Clinical Study Register
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带注释的病例报告表
信息标识符:112483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:112483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:112483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:112483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:112483信息评论:For additional information about this study please refer to the GSK Clinical Study Register
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