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24-week Trial Comparing GSK573719/GW642444 With GW642444 and With Tiotropium in Chronic Obstructive Pulmonary Disease

2018年1月18日 更新者：GlaxoSmithKline

A Multicenter Trial Comparing the Efficacy and Safety of GSK573719/GW642444 With GW642444 and With Tiotropium Over 24 Weeks in Subjects With COPD

This is a Phase III multicenter, randomized, double-blind, double-dummy, parallel-group study to evaluate the efficacy and safety of two doses of GSK573719/GW642444 Inhalation Powder and GW642444 Inhalation Powder via a Novel Dry Powder Inhaler and tiotropium via HandiHaler when administered once-daily over a 24-week treatment period in subjects with chronic obstructive pulmonary disease (COPD). Subjects who meet eligibility criteria at Screening (Visit 1) will complete a 7 to10 day run-in period followed by a randomization visit (Visit 2) then a 24-week treatment period. There will be a total of 9 clinic study visits. A follow-up phone contact for adverse event assessment will be conducted approximately one week after the last study visit (Visit 9 or Early Withdrawal). The total duration of subject participation in the study will be approximately 26 weeks. The primary measure of efficacy is clinic visit trough (pre-bronchodilator and pre-dose) forced expiratory volume in one second (FEV1) on Treatment Day 169. Safety will be assessed by adverse events, 12-lead ECGs, vital signs, and clinical laboratory tests.

研究概览

地位

完全的

条件

干预/治疗

详细说明

This is a 24-week, Phase III multicenter, randomized, double-blind, double-dummy, parallel-group study. Eligible subjects will be randomized to GSK573719/GW642444 125/25mcg, GSK573719/GW642444 62.5/25mcg, GW642444 25mcg, or tiotropium treatment groups in a 1:1:1:1 ratio. Treatments will be administered once-daily in the morning by inhalation using a Novel Dry Powder Inhaler (Novel DPI) and HandiHaler. There will be a total of 9 study clinic visits conducted on an outpatient basis. Subjects who meet the eligibility criteria at Screening (Visit 1) will complete a 7 to 10 day run-in period followed by a 24-week treatment period. Clinic visits will be at Screening, Randomization (Day 1), Day 2, after 4, 8, 12, 16, and 24-weeks of treatment, and 1 day after the Week 24 Visit (also referred as Treatment Day 169). A follow-up contact for adverse assessment will be conducted by telephone approximately 7 days after Visit 9 or the Early Withdrawal Visit. The total duration of subject participation, including follow-up will be approximately 26 weeks. All subjects will be provided with albuterol/salbutamol for use on an "as-needed" basis throughout the run-in and study treatment periods. At screening, pre-bronchodilator spirometry testing will be followed by post-albuterol/salbutamol spirometry testing. Post-albuterol/salbutamol FEV1 and FEV1/forced vital capacity (FVC) values will be used to determine subject eligibility. To further characterize bronchodilator responsiveness, post-ipratropium testing will be conducted following completion of post-albuterol/salbutamol spirometry. Spirometry will be conducted at each post-randomization clinic visit. Six hour post-dose serial spirometry will be conducted at Visits 2, 6, and 8. Trough spirometry will be obtained 23 and 24 hours after the previous day's dose of blinded study medication at Visits 3 to 9. All subjects will be provided with an electronic diary (eDiary) for completion daily in the morning and the evening throughout the run-in and treatment periods. Subjects will use the eDiary to record peak expiratory flow (PEF) each morning, dyspnea scores using the Shortness of Breath with Daily Activities instrument (SOBDA), daily use of supplemental albuterol/salbutamol as either puffs/day from a metered-dose inhaler (MDI) and/or nebules used per day, and any healthcare contacts related to COPD. Additional assessments of dyspnea will be obtained using the Baseline and Transition Dyspnea Index (BDI/TDI) which is an interviewer based instrument. At Visit 2, the severity of dyspnea at baseline will be assessed using the BDI. At subsequent visits (Visits 4, 6, and 8) change from baseline will be assessed using the TDI. General health status will be evaluated using the subject-completed EQ-5D questionnaire at Visits 2, 4, 6, and 8. Disease specific health status will be evaluated using the subject-completed St. George's Respiratory Questionnaire (SGRQ) at Visits 2, 4, 6, and 8, and the subject-completed COPD Assessment Test (CAT) at Visits 2, 6, and 8. The occurrence of adverse events will be evaluated throughout the study beginning at Visit 2. SAEs will be collected over the same time period as for AEs. However, any SAEs assessed as related to study participation (e.g., study treatment, protocol-mandated procedures, invasive tests, or change in existing therapy) or related to a GSK concomitant medication, will be recorded from the time a subject consents to participate in the study up to and including any follow up contact. Additional safety assessments of vital signs (blood pressure and pulse rate), 12-lead ECGs and standard clinical laboratory tests (hematology and chemistry) will be obtained at selected clinic visits.

研究类型

介入性

注册 (实际的)

846

阶段

  • 第三阶段

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

  • 乌克兰
      • Dnipropetrovsk、乌克兰、49074
        • GSK Investigational Site
      • Dnipropetrovsk、乌克兰、49027
        • GSK Investigational Site
      • Donetsk、乌克兰、83099
        • GSK Investigational Site
      • Ivano-Frankivsk、乌克兰、76018
        • GSK Investigational Site
      • Kharkiv、乌克兰、61124
        • GSK Investigational Site
      • Kharkiv、乌克兰、61037
        • GSK Investigational Site
      • Kiev、乌克兰、03680
        • GSK Investigational Site
      • Kyiv、乌克兰、03680
        • GSK Investigational Site
      • Kyiv、乌克兰、03038
        • GSK Investigational Site
      • Kyiv、乌克兰、01114
        • GSK Investigational Site
      • Simferopol、乌克兰、95043
        • GSK Investigational Site
      • Vinnytsia、乌克兰、21029
        • GSK Investigational Site
      • Zaporizhia、乌克兰、69035
        • GSK Investigational Site
  • 俄罗斯联邦
      • Chita、俄罗斯联邦、672000
        • GSK Investigational Site
      • Irkutsk、俄罗斯联邦、664005
        • GSK Investigational Site
      • Moscow、俄罗斯联邦、115446
        • GSK Investigational Site
      • Petrozavodsk、俄罗斯联邦、185019
        • GSK Investigational Site
      • Ryazan、俄罗斯联邦、390039
        • GSK Investigational Site
      • Saint-Petersburg、俄罗斯联邦、194354
        • GSK Investigational Site
      • Saratov、俄罗斯联邦、410028
        • GSK Investigational Site
      • Saratov、俄罗斯联邦、410018
        • GSK Investigational Site
      • Tomsk、俄罗斯联邦、634001
        • GSK Investigational Site
      • Voronezh、俄罗斯联邦、394018
        • GSK Investigational Site
      • Yaroslavl、俄罗斯联邦
        • GSK Investigational Site
  • 墨西哥
      • Mexico、墨西哥、10700
        • GSK Investigational Site
      • Mexico City、墨西哥、07760
        • GSK Investigational Site
    • Jalisco
      • Guadalajara、Jalisco、墨西哥、44100
        • GSK Investigational Site
      • Zapopan、Jalisco、墨西哥、45200
        • GSK Investigational Site
  • 德国
      • Berlin、德国、13086
        • GSK Investigational Site
      • Berlin、德国、10717
        • GSK Investigational Site
      • Berlin、德国、12203
        • GSK Investigational Site
      • Berlin、德国、12157
        • GSK Investigational Site
      • Hamburg、德国、22299
        • GSK Investigational Site
    • Baden-Wuerttemberg
      • Sinsheim、Baden-Wuerttemberg、德国、74889
        • GSK Investigational Site
      • Stuttgart、Baden-Wuerttemberg、德国、70378
        • GSK Investigational Site
    • Bayern
      • Bamberg、Bayern、德国、96049
        • GSK Investigational Site
      • Erlangen、Bayern、德国、91052
        • GSK Investigational Site
      • Muenchen、Bayern、德国、80339
        • GSK Investigational Site
      • Nuernberg、Bayern、德国、90402
        • GSK Investigational Site
    • Brandenburg
      • Potsdam、Brandenburg、德国、14467
        • GSK Investigational Site
    • Hessen
      • Marburg、Hessen、德国、35037
        • GSK Investigational Site
    • Niedersachsen
      • Hannover、Niedersachsen、德国、30159
        • GSK Investigational Site
      • Hannover、Niedersachsen、德国、30173
        • GSK Investigational Site
    • Nordrhein-Westfalen
      • Dortmund、Nordrhein-Westfalen、德国、44263
        • GSK Investigational Site
      • Dortmund、Nordrhein-Westfalen、德国、44147
        • GSK Investigational Site
  • 意大利
    • Campania
      • Avellino、Campania、意大利、83100
        • GSK Investigational Site
    • Friuli-Venezia-Giulia
      • Pordenone、Friuli-Venezia-Giulia、意大利、33170
        • GSK Investigational Site
    • Lazio
      • Roma、Lazio、意大利、00144
        • GSK Investigational Site
    • Liguria
      • Pietra Ligure (SV)、Liguria、意大利、17027
        • GSK Investigational Site
    • Lombardia
      • Milano、Lombardia、意大利、20121
        • GSK Investigational Site
      • Pavia、Lombardia、意大利、27100
        • GSK Investigational Site
      • Tradate (VA)、Lombardia、意大利、21049
        • GSK Investigational Site
    • Puglia
      • Foggia、Puglia、意大利、71100
        • GSK Investigational Site
    • Sicilia
      • Catania、Sicilia、意大利、95123
        • GSK Investigational Site
    • Toscana
      • Pisa、Toscana、意大利、56124
        • GSK Investigational Site
  • 法国
      • Clermont Ferrand cedex 1、法国、63003
        • GSK Investigational Site
      • Nantes cedex 1、法国、44093
        • GSK Investigational Site
      • Nîmes cedex 09、法国、30029
        • GSK Investigational Site
      • Saint Pierre Cedex、法国、97448
        • GSK Investigational Site
  • 波兰
      • Gdansk、波兰、80-405
        • GSK Investigational Site
      • Gidle、波兰、97-540
        • GSK Investigational Site
      • Krakow、波兰、31-023
        • GSK Investigational Site
      • Lubliniec、波兰、42-700
        • GSK Investigational Site
      • Sopot、波兰、81-741
        • GSK Investigational Site
      • Wloclawek、波兰、87-800
        • GSK Investigational Site
      • Zabrze、波兰、41-800
        • GSK Investigational Site
  • 秘鲁
      • Callao、秘鲁、Callao 2
        • GSK Investigational Site
      • Lima、秘鲁、Lima 1
        • GSK Investigational Site
    • Lima
      • Jesus Maria、Lima、秘鲁、Lima 11
        • GSK Investigational Site
      • Lima 27、Lima、秘鲁、Lima 27
        • GSK Investigational Site
      • San Borja、Lima、秘鲁、Lima 41
        • GSK Investigational Site
      • San Isidro、Lima、秘鲁、Lima 27
        • GSK Investigational Site
      • San Miguel、Lima、秘鲁、Lima 32
        • GSK Investigational Site
      • Santiago de Surco、Lima、秘鲁、Lima 33
        • GSK Investigational Site
  • 罗马尼亚
      • Bacau、罗马尼亚、600252
        • GSK Investigational Site
      • Bucharest、罗马尼亚、011794
        • GSK Investigational Site
      • Ploiesti、罗马尼亚、100184
        • GSK Investigational Site
      • Timisoara、罗马尼亚、300310
        • GSK Investigational Site
  • 美国
    • Alabama
      • Birmingham、Alabama、美国、35216
        • GSK Investigational Site
    • California
      • San Diego、California、美国、92117
        • GSK Investigational Site
    • Florida
      • DeLand、Florida、美国、32720
        • GSK Investigational Site
      • Orlando、Florida、美国、32822
        • GSK Investigational Site
      • Tampa、Florida、美国、33603
        • GSK Investigational Site
    • Georgia
      • Decatur、Georgia、美国、30033
        • GSK Investigational Site
    • Missouri
      • Saint Charles、Missouri、美国、63301
        • GSK Investigational Site
    • New Mexico
      • Albuquerque、New Mexico、美国、87108
        • GSK Investigational Site
    • Oklahoma
      • Oklahoma City、Oklahoma、美国、73103
        • GSK Investigational Site
    • Pennsylvania
      • Phoenixville、Pennsylvania、美国、19460
        • GSK Investigational Site
    • South Carolina
      • Charleston、South Carolina、美国、29406-7108
        • GSK Investigational Site
      • Gaffney、South Carolina、美国、29340
        • GSK Investigational Site
      • Greenville、South Carolina、美国、29615
        • GSK Investigational Site
      • Rock Hill、South Carolina、美国、29732
        • GSK Investigational Site
      • Seneca、South Carolina、美国、29678
        • GSK Investigational Site
    • South Dakota
      • Rapid City、South Dakota、美国、57702
        • GSK Investigational Site
    • Texas
      • San Antonio、Texas、美国、78229
        • GSK Investigational Site
    • Virginia
      • Newport News、Virginia、美国、23606
        • GSK Investigational Site
      • Richmond、Virginia、美国、23229
        • 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

40年 及以上 (成人、年长者)

接受健康志愿者

不

有资格学习的性别

全部

描述

Inclusion Criteria:

  • outpatient
  • signed and dated written informed consent
  • 40 years of age or older
  • male and female subjects
  • COPD diagnosis
  • at least 10 pack-year smoking history
  • post-albuterol/salbutamol FEV1/FVC ratio of <0.70 and post-albuterol/salbutamol FEV1 of less than or equal to 70% predicted normal values
  • score of greater than or equal to 2 on the Modified Medical Resarch Council Dyspnea Scale (mMRC)

Exclusion Criteria:

  • women who are pregnant or lactating or are planning on becoming pregnant during the study
  • current diagnosis of asthma
  • other respiratory disorders other than COPD
  • other diseases/abnormalities that are uncontrolled including cancer not in remission for at least 5 years
  • chest x-ray or CT scan with clinically significant abnormalities not believed to be due to COPD
  • hypersensitivity to anticholinergics, beta-agonists, lactose/milk protein or magnesium stearate or medical conditions associated with inhaled anticholinergics
  • hospitalization for COPD or pneumonia within 12 weeks prior to Visit 1
  • lung volume reduction surgery within 12 months prior to Visit 1
  • abnormal and clinically significant ECG at Visit 1
  • significantly abnormal finding from laboratory tests at Visit 1
  • unable to withhold albuterol/salbutamol at least 4 hours prior to spirometry at each visit
  • use of depot corticosteroids within 12 weeks of Visit 1
  • use of oral or parenteral corticosteroids, antibiotics for lower respiratory tract infection, or cytochrome P450 3A4 inhibitors, within 6 weeks of Visit 1
  • use of long-acting beta-agonist (LABA)/inhaled corticosteroid (ICS) product if LABA/ICS therapy is discontinued withing 30 days of Visit 1
  • use of ICS at a dose of >1000mcg/day of fluticasone propionate or equivalent within 30 days of Visit 1
  • initiation or discontinuation of ICS within 30 days of Visit 1
  • use of tiotropium or roflumilast within 14 days of Visit 1
  • use of theophyllines, oral leukotriene inhibitors, long-acting oral beta-agonists, or inhaled long-acting beta-agonists within 48 hours of Visit 1
  • short-acting oral beta-agonists within 12 hours of Visit 1
  • use of LABA/ICS combination products only if discontinuing LABA therapy and switching to ICS monotherapy within 48 hours of Visit 1 for the LABA component
  • use of sodium cromoglycate or nedocromil sodium within 24 hours of Visit 1
  • use of inhaled short-acting beta-agonists, inhaled short-acting anticholinergics, or inhaled short-acting anticholinergic/short-acting beta-agonist combination products within 4 hours of Visit 1
  • use of any other investigational medication within 30 days or 5 drug half-lives (whichever is longer)
  • long-term oxygen therapy prescribed for >12 hours per day
  • regular use of nebulized short-acting bronchodilators
  • participation in acute phase of pulmonary rehabilitation program
  • known or suspected history of alcohol or drug abse within 2 years prior to Visit 1
  • anyone affiliated with the investigator site (e.g., investigator, sub-investigator, study coordinator, employee of a participating investigator or study site, or immediate family member)
  • previous exposure to GSK573719, GSK573719/GW642444 combination, GW642444 (vilanterol), or fluticasone furoate/GW642444 combination

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：四人间

武器和干预

参与者组/臂
干预/治疗
实验性的：GSK573719/GW642444 125/25
125/25 微克每天一次
药品：GSK573719/GW642444 125/25
125/25 微克每天一次
其他名称：
  • GSK573719/维兰特罗三氟甲酸酯
实验性的：GSK573719/GW642444 62.5/25
62.5/25 微克，每日一次
药品：GSK573719/GW642444 62.5/25
62.5/26 mcg once-daily
其他名称：
  • GSK573719/维兰特罗三氟甲酸酯
有源比较器：噻托溴铵
每天一次 18 微克
药品：噻托溴铵
每天一次 18 微克
实验性的：GW642444
25 mcg once-daily
药品：GW642444
25 mcg once-daily
其他名称：
  • vilanterol trifenatate

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
Change From Baseline (BL) in Trough Forced Expiratory Volume in One Second (FEV1) on Day 169 (Week 24)
大体时间：Baseline and Day 169
FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. Trough FEV1 measurements were taken electronically by spirometry on Days 2, 28, 56, 84, 112, 168, and 169. Baseline is defined as the mean of the assessments made 30 minutes pre-dose and 5 minutes pre-dose on Treatment Day 1. Trough FEV1 is defined as the mean of the FEV1 values obtained at 23 and 24 hours after the previous morning's dosing (ie., trough FEV1 on Day 169 is the mean of the FEV1 values obtained 23 and 24 hours after the morning dosing on Day 168). Change from Baseline at a particular visit was calculated as the trough FEV1 at that visit minus Baseline. Analysis was performed using a repeated measures model with covariates of treatment, Baseline , smoking status, center group, day, and day by Baseline and day by treatment interactions. ITT=Intent-to-Treat; par.=participants. .
Baseline and Day 169

次要结果测量

结果测量
措施说明
大体时间
第 168 天给药后获得的加权平均值 (WM) 0-6 小时 FEV1 相对于基线 (BL) 的变化
大体时间：基线和第 168 天
FEV1 是衡量肺功能的指标，定义为一秒钟内可以用力呼出的最大空气量。 WM FEV1 是通过使用梯形法则计算 FEV1/时间曲线 (AUC) 下的面积，然后将该值除以计算 AUC 的时间间隔得出的。 在第 1 天、第 84 天和第 168 天使用当天收集的 0-6 小时给药后 FEV1 测量值计算 WM，其中包括给药前（第 1 天：给药前 30 分钟 [分钟] 和 5 分钟） ；其他连续访问：前一早间服药后 23 和 24 小时）和服药后 15 分钟、30 分钟、1 小时、3 小时和 6 小时。 特定访问时 BL 的变化计算为该访问时的 WM 减去 BL。 使用具有治疗协变量的重复测量模型进行分析，BL（在第 1 天给药前 30 分钟和 5 分钟进行的两次评估的平均值），吸烟状况，中心组，天数，BL 天数和治疗天数相互作用。
基线和第 168 天

其他结果措施

结果测量
措施说明
大体时间
第 24 周的日常活动呼吸急促 (SOBDA) 评分相对于基线 (BL) 的变化
大体时间：基线和第 24 周
新开发的 SOBDA 问卷评估日常活动时的呼吸困难或呼吸急促 (SOB)。 SOBDA 问卷由参与者（par.）每晚睡前完成的 13 个项目组成，当 par.指示反思当天的活动。 每日得分计算为 13 个项目得分的平均值（>=7 个项目必须具有非缺失响应才能计算）。 标准杆。根据 7 天数据的平均值（必须完成 7 天中的 >=4 才能计算每周平均值），每周平均 SOBDA 评分范围从 1 到 4（分数越高表示日常活动时呼吸困难越严重） . BL 的变化是平均每周 SOBDA 分数减去 BL。 使用 MMRM 与治疗协变量、BL（治疗前一周的平均得分）、吸烟状况、中心组、周、BL 周和治疗交互作用周进行分析。 此 MMRM 分析仅包括第 4、8、12 和 24 周。
基线和第 24 周

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。

赞助

GlaxoSmithKline

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。

一般刊物

有用的网址

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

2011年3月1日

初级完成 (实际的)

2012年4月1日

研究完成 (实际的)

2012年4月24日

研究注册日期

首次提交

2011年3月15日

首先提交符合 QC 标准的

2011年3月15日

首次发布 (估计)

2011年3月16日

研究记录更新

最后更新发布 (实际的)

2018年1月24日

上次提交的符合 QC 标准的更新

2018年1月18日

最后验证

2018年1月1日

更多信息

与本研究相关的术语

关键字

其他相关的 MeSH 术语

其他研究编号

  • 113360

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

  1. 统计分析计划
    信息标识符：113360
    信息评论：For additional information about this study please refer to the GSK Clinical Study Register
  2. 临床研究报告
    信息标识符：113360
    信息评论：For additional information about this study please refer to the GSK Clinical Study Register
  3. 数据集规范
    信息标识符：113360
    信息评论：For additional information about this study please refer to the GSK Clinical Study Register
  4. 带注释的病例报告表
    信息标识符：113360
    信息评论：For additional information about this study please refer to the GSK Clinical Study Register
  5. 研究协议
    信息标识符：113360
    信息评论：For additional information about this study please refer to the GSK Clinical Study Register
  6. 知情同意书
    信息标识符：113360
    信息评论：For additional information about this study please refer to the GSK Clinical Study Register
  7. 个人参与者数据集
    信息标识符：113360
    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.

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