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Effect of GSK1160724 In Healthy Volunteers

2017年9月5日 更新者:GlaxoSmithKline

A Randomized Double-blind, Placebo-controlled, Crossover, Dose Escalation Study to Examine the Safety, Tolerability, Pharmacodynamics and Pharmacokinetics of Single Inhaled Doses of GSK1160724 and Tiotropium Bromide

GSK1160724 is a potent mAChR antagonist, which is being developed for treatment of chronic obstructive pulmonary disease (COPD)

研究概览

研究类型

介入性

注册 (实际的)

21

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

    • Middlesex
      • Harrow、Middlesex、英国、HA1 3UJ
        • GSK Investigational Site

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

是的

有资格学习的性别

全部

描述

Inclusion Criteria:

  • Healthy male and female subjects. Female subjects must be of non-child bearing potential.
  • Aged between 18-55 years inclusive
  • Non-smokers
  • Normal spirometry
  • A signed and dated written informed consent is obtained from the subject
  • The subject is capable of giving informed consent, which includes compliance with the requirements and restrictions listed in the consent form
  • Available to complete the study
  • The subject is greater than or equal to 50kg with a body mass index within the range 19.0 to 29.9 kg/m2 inclusive
  • Response to ipratropium bromide

Exclusion Criteria:

  • Any clinically relevant and important abnormality identified at the screening medical assessment (physical examination/medical history), clinical laboratory tests, or ECG (12-lead or Holter)
  • A history of breathing problems
  • A mean QTc(B) value > 450ms, the QTc(B) of the 3 screening ECGs are not within 10% of the mean, a PR interval outside the range 90-210ms or an ECG that is not suitable for QT measurements at screening
  • A history of elevated resting blood pressure or a mean blood pressure higher than 140/90 mmHg at screening
  • A mean heart rate outside the range 40-90 bpm inclusive at screening
  • History of use of tobacco- or nicotine-containing products within 6 months of screening, and/or positive urine cotinine test results at screening
  • Where participation in the study would result in donation of blood in excess of 500mL within a 56 day period at screening
  • The subject is currently taking regular (or a course of) medication, whether prescribed or not, including herbal remedies such as St John's Wort etc.

The subject has taken:

  • prescription medications for 14 days prior to first dose of study drug, or
  • Over-the-counter (OTC) medications/preparations (including herbal remedies, etc.) excluding simple analgesics for 48 hours prior to first dose of study drug,unless it is judged by the Investigator not to compromise the subject's safety or influence the outcome of the study.
  • The subject has participated in a study with a new molecular entity or any other trial within a period of 3 months prior first dose of study drug
  • The subject has tested positive for hepatitis C antibody (third generation enzyme immunoassay), hepatitis B surface antigen or HIV antibodies (if tested according to site SOP's) at screening.
  • The subject has tested positive for drugs-of-abuse at screening
  • The subject has tested positive for urine alcohol (including ethanol) at screening The detection of alcohol would not be an exclusion at screening but would need to be negative pre-dose and during the study
  • The subject is unable to use the DISKUS™ and/or HandiHaler inhaler devices correctly at screening
  • The subject has a suspected history of alcohol abuse within the six months previous to the screening visit
  • The subject has a known allergy or hypersensitivity to magnesium stearate, milk protein or the excipient lactose monohydrate, iodine, ipratropium bromide, tiotropium bromide, atropine and/or any of its derivatives
  • The subject has a significant clinical history of prostatic hypertrophy or narrow angle glaucoma
  • The subject has received an allogeneic bone marrow transplant
  • The subject has claustrophobia that may be aggravated by entering the whole body plethysmography cabinet

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:交叉作业

武器和干预

参与者组/臂
干预/治疗
实验性的:All subjects
Eligible subjects will receive one of the following treatment in cohort I and cohort II in five different treatment periods; Placebo, GSK1160724 (10 micrograms, 50 micrograms or 125 micrograms) and tiotropium bromide
受试者将接受安慰剂。
GSK1160724 will be available with dosing strengths of 10, 50 and 125 micrograms/blister for inhalation using the DISKUS inhaler.
Tiotropium bromide capsules will be supplied with a dose of 18 micrograms administered via a HandiHaler device.

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
Number of subjects with adverse events (AEs)
大体时间:Up to Week 24
An AE is any untoward medical occurrence in a clinical study subjects, temporally associated with the use of a study treatment, whether or not considered related to the study treatment.
Up to Week 24
Number of subjects with abnormal values for blood pressure
大体时间:Up to Week 24
Systolic and diastolic blood pressure will be measured in a semi-recumbent position after 5 minutes rest.
Up to Week 24
Number of subjects with abnormal values for heart rate
大体时间:Up to Week 24
Heart rate will be measured in a semi-recumbent position after 5 minutes rest.
Up to Week 24
Number of subjects with abnormal electrocardiogram (ECG) findings
大体时间:Up to Week 24
Triplicate 12-lead ECGs will be measured in a semi-recumbent position after 5 minutes rest at each time point using ECG machine.
Up to Week 24
Number of subjects with abnormal findings after holter monitoring
大体时间:Up to 24 hour
Holter monitoring will be conducted at 24 hour.
Up to 24 hour
Forced expiratory volume in 1 second (FEV1)
大体时间:Up to Week 24
Lung function will be measured by FEV1, defined as the maximal amount of air that can be forcefully exhaled in one second.
Up to Week 24
Forced vital capacity (FVC)
大体时间:Up to Week 24
Lung function will be measured by FVC, defined as the amount of air which can be forcibly exhaled from the lungs after taking the deepest breath possible.
Up to Week 24
Number of subjects having abnormal hematology laboratory parameters
大体时间:Up to Week 24
Hematology parameters will be assessed as a measure of safety.
Up to Week 24
Number of subjects with abnormal clinical chemistry parameters
大体时间:Up to Week 24
Clinical parameters will be assessed as a measure of safety.
Up to Week 24
Number of subjects with abnormal values for urinalysis
大体时间:Up to Week 24
Urinalysis will be performed as a measure of safety.
Up to Week 24
Maximum value for resting heart rate over 0-4 hour
大体时间:Up to 4 hours
Maximum value for heart rate over 0-4 hour will be determined.
Up to 4 hours
Maximum value for resting blood pressure over 0-4 hour
大体时间:Up to 4 hours
Maximum value for resting systolic and diastolic blood pressure over 0-4 hour will be determined.
Up to 4 hours
Maximum value for resting ECG over 0-4 hour
大体时间:Up to 4 hours
Maximum value for resting ECG over 0-4 hour will be determined.
Up to 4 hours
Weighted mean of resting heart rate over 0-4 hour
大体时间:Up to 4 hours
Weighted mean for resting heart rate over 0-4 hour will be determined.
Up to 4 hours
Weighted mean of resting blood pressure over 0-4 hour
大体时间:Up to 4 hours
Weighted mean for resting systolic and diastolic blood pressure over 0-4 hour will be determined.
Up to 4 hours
Weighted mean of resting ECG over 0-4 hour
大体时间:Up to 4 hours
Weighted mean for resting resting ECG over 0-4 hour will be determined.
Up to 4 hours

次要结果测量

结果测量
措施说明
大体时间
Plasma concentrations of GSK1160724
大体时间:Pre-dose, 5 minutes, 15 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6 hours, 8 hours.12 hours, 16 hours, 24 hours, 48 hours Post-dose
Plasma samples will be collected at the indicated time points to measure the concentration of GSK1160724.
Pre-dose, 5 minutes, 15 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6 hours, 8 hours.12 hours, 16 hours, 24 hours, 48 hours Post-dose
Plasma concentrations of GSK1762245
大体时间:Pre-dose, 5 minutes, 15 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6 hours, 8 hours.12 hours, 16 hours, 24 hours, 48 hours Post-dose
Plasma samples will be collected at the indicated time points to measure the concentration of the active metabolite GSK1762245.
Pre-dose, 5 minutes, 15 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6 hours, 8 hours.12 hours, 16 hours, 24 hours, 48 hours Post-dose
Urine concentrations of GSK1160724
大体时间:0-2 hours, 2-8 hours, 8-12 hours and 12-24 hours
Urine samples will be collected at the indicated time points to measure the concentration of GSK1160724.
0-2 hours, 2-8 hours, 8-12 hours and 12-24 hours
Urine concentrations of GSK1762245
大体时间:0-2 hours, 2-8 hours, 8-12 hours and 12-24 hours
Urine samples will be collected at the indicated time points to measure the concentration of the active metabolite GSK1762245.
0-2 hours, 2-8 hours, 8-12 hours and 12-24 hours
Maximum observed concentration (Cmax) of GSK1160724
大体时间:Pre-dose, 5 minutes, 15 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6 hours, 8 hours.12 hours, 16 hours, 24 hours, 48 hours Post-dose
Blood samples will be collected at the indicated time points for pharmacokinetic analysis.
Pre-dose, 5 minutes, 15 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6 hours, 8 hours.12 hours, 16 hours, 24 hours, 48 hours Post-dose
Cmax of GSK1762245
大体时间:Pre-dose, 5 minutes, 15 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6 hours, 8 hours.12 hours, 16 hours, 24 hours, 48 hours Post-dose
Blood samples will be collected at the indicated time points for pharmacokinetic analysis.
Pre-dose, 5 minutes, 15 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6 hours, 8 hours.12 hours, 16 hours, 24 hours, 48 hours Post-dose
Time to Cmax (Tmax) of GSK1160724
大体时间:Pre-dose, 5 minutes, 15 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6 hours, 8 hours.12 hours, 16 hours, 24 hours, 48 hours Post-dose
Blood samples will be collected at the indicated time points for pharmacokinetic analysis.
Pre-dose, 5 minutes, 15 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6 hours, 8 hours.12 hours, 16 hours, 24 hours, 48 hours Post-dose
Tmax of GSK1762245
大体时间:Pre-dose, 5 minutes, 15 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6 hours, 8 hours.12 hours, 16 hours, 24 hours, 48 hours Post-dose
Blood samples will be collected at the indicated time points for pharmacokinetic analysis.
Pre-dose, 5 minutes, 15 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6 hours, 8 hours.12 hours, 16 hours, 24 hours, 48 hours Post-dose
Time to last observed plasma concentration (Tlast) of GSK1160724
大体时间:Pre-dose, 5 minutes, 15 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6 hours, 8 hours.12 hours, 16 hours, 24 hours, 48 hours Post-dose
Blood samples will be collected at the indicated time points for pharmacokinetic analysis.
Pre-dose, 5 minutes, 15 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6 hours, 8 hours.12 hours, 16 hours, 24 hours, 48 hours Post-dose
Tlast of GSK1762245
大体时间:Pre-dose, 5 minutes, 15 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6 hours, 8 hours.12 hours, 16 hours, 24 hours, 48 hours Post-dose
Blood samples will be collected at the indicated time points for pharmacokinetic analysis.
Pre-dose, 5 minutes, 15 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6 hours, 8 hours.12 hours, 16 hours, 24 hours, 48 hours Post-dose
Area under the plasma concentration time curve from time 0 to last time of quantifiable concentration (AUC [0-T]) of GSK1160724
大体时间:Pre-dose, 5 minutes, 15 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6 hours, 8 hours.12 hours, 16 hours, 24 hours, 48 hours Post-dose
Blood samples will be collected at the indicated time points for pharmacokinetic analysis.
Pre-dose, 5 minutes, 15 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6 hours, 8 hours.12 hours, 16 hours, 24 hours, 48 hours Post-dose
AUC (0-T) of GSK1762245
大体时间:Pre-dose, 5 minutes, 15 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6 hours, 8 hours.12 hours, 16 hours, 24 hours, 48 hours Post-dose
Blood samples will be collected at the indicated time points for pharmacokinetic analysis.
Pre-dose, 5 minutes, 15 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6 hours, 8 hours.12 hours, 16 hours, 24 hours, 48 hours Post-dose
Area under the plasma concentration time curve from time 0 to infinity (AUC [0-infinity]) of GSK1160724
大体时间:Pre-dose, 5 minutes, 15 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6 hours, 8 hours.12 hours, 16 hours, 24 hours, 48 hours Post-dose
Blood samples will be collected at the indicated time points for pharmacokinetic analysis.
Pre-dose, 5 minutes, 15 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6 hours, 8 hours.12 hours, 16 hours, 24 hours, 48 hours Post-dose
AUC (0-infinity) of GSK1762245
大体时间:Pre-dose, 5 minutes, 15 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6 hours, 8 hours.12 hours, 16 hours, 24 hours, 48 hours Post-dose
Blood samples will be collected at the indicated time points for pharmacokinetic analysis.
Pre-dose, 5 minutes, 15 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6 hours, 8 hours.12 hours, 16 hours, 24 hours, 48 hours Post-dose
The terminal phase elimination rate constant (Lambda z) of GSK1160724
大体时间:Pre-dose, 5 minutes, 15 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6 hours, 8 hours.12 hours, 16 hours, 24 hours, 48 hours Post-dose
Blood samples will be collected at the indicated time points for pharmacokinetic analysis.
Pre-dose, 5 minutes, 15 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6 hours, 8 hours.12 hours, 16 hours, 24 hours, 48 hours Post-dose
Lambda z of GSK1762245
大体时间:Pre-dose, 5 minutes, 15 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6 hours, 8 hours.12 hours, 16 hours, 24 hours, 48 hours Post-dose
Blood samples will be collected at the indicated time points for pharmacokinetic analysis.
Pre-dose, 5 minutes, 15 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6 hours, 8 hours.12 hours, 16 hours, 24 hours, 48 hours Post-dose
The Terminal phase half life (T1/2) of GSK1160724
大体时间:Pre-dose, 5 minutes, 15 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6 hours, 8 hours.12 hours, 16 hours, 24 hours, 48 hours Post-dose
Blood samples will be collected at the indicated time points for pharmacokinetic analysis.
Pre-dose, 5 minutes, 15 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6 hours, 8 hours.12 hours, 16 hours, 24 hours, 48 hours Post-dose
T1/2 of GSK1762245
大体时间:Pre-dose, 5 minutes, 15 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6 hours, 8 hours.12 hours, 16 hours, 24 hours, 48 hours Post-dose
Blood samples will be collected at the indicated time points for pharmacokinetic analysis.
Pre-dose, 5 minutes, 15 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6 hours, 8 hours.12 hours, 16 hours, 24 hours, 48 hours Post-dose
Serial specific airway conductance (sGaw) response over 24 hours post-dose of GSK1160724 and tiotropium bromide
大体时间:Up to 24 hours
The sGaw response will be assessed by whole body plethysmograph at the indicated timepoints.
Up to 24 hours
FEV1 over 24 hours post-dose of GSK1160724 and tiotropium bromide
大体时间:Up to 24 hours
The sGaw response will be assessed by whole body plethysmograph at the indicated timepoints.
Up to 24 hours
FVC over 24 hours post-dose of GSK1160724 and tiotropium bromide
大体时间:Up to 24 hours
The sGaw response will be assessed by whole body plethysmograph at the indicated timepoints.
Up to 24 hours
Serial sGaw measurements over 48 hours of GSK1160724 and tiotropium bromide
大体时间:Up to 48 hours
The sGaw is a measure of the change in specific airway conductance. It will be assessed by whole body plethysmograph at the indicated timepoints.
Up to 48 hours

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。

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)

2007年12月12日

初级完成 (实际的)

2008年4月7日

研究完成 (实际的)

2008年4月7日

研究注册日期

首次提交

2007年11月6日

首先提交符合 QC 标准的

2007年11月6日

首次发布 (估计)

2007年11月7日

研究记录更新

最后更新发布 (实际的)

2017年9月8日

上次提交的符合 QC 标准的更新

2017年9月5日

最后验证

2017年9月1日

更多信息

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.

安慰剂的临床试验

3
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