A12-Week, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of GSK573719 Delivered Once-Daily Via a Novel Dry Powder Inhaler in Subjects With Chronic Obstructive Pulmonary Disease
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 206
- 试验地点
- 1
- 主要终点
- Change From Baseline (BL) in Trough Forced Expiratory Volume in One Second (FEV1) on Day 85
研究概览
简要总结
The purpose of this study is to assess if 12 weeks' treatment with GSK573719 Inhalation Powder is safe and effective compared with placebo or no active drug intake, when administered once-daily in subjects with Chronic Obstructive Pulmonary Disease (COPD).
详细描述
Inhaled bronchodilators, such as beta 2 agonists and anticholinergics, and inhaled corticosteroids are the mainstays of therapy in patients diagnosed with COPD. Anticholinergic bronchodilators or long acting muscarinic receptor antagonists function by blocking endogenous airway smooth muscle cholinergic tone. Treatment with anticholinergics has been shown to significantly improve forced expiratory volume in 1 second (FEV1), resting and dynamic lung hyperinflation, symptoms, and exercise capacity in patients with COPD. Currently tiotropium is the only approved long acting muscarinic antagonist available for treatment of COPD.This is a multicenter, randomized, double-blind, placebo-controlled, parallel group study to evaluate the efficacy and safety of GSK573719 Inhalation Powder of 2 doses when administered once-daily via Novel DPI compared with placebo over a treatment period of 12 weeks in subjects with COPD. There will be a total of 8 study clinic visits conducted on an outpatient basis. Subjects who meet the eligibility criteria at Screening (Visit 1) will complete a 5 to 9 days run-in period followed by a 12-week treatment period. There will be 8 clinic visits during three of which serial spirometry will be performed . The total duration of subject participation in the study will be approximately 14 weeks.
This is a Phase III multicenter, randomized, double-blind, placebo-controlled, parallel group study to evaluate the efficacy and safety of GSK573719 Inhalation Powder 62.5 mcg and 125 mcg when administered once-daily via Novel DPI compared with placebo over a treatment period of 12 weeks in subjects with COPD.
Eligible subjects will be randomized 1:1:1 to receive either of the two doses of GSK573719 Inhalation Powder doses or placebo for 12 weeks.
There will be a total of 8 study clinic visits conducted on an outpatient basis. Subjects who meet the eligibility criteria at Screening (Visit 1) will complete a 5 to 9 days run-in period followed by a 12-week treatment period. Clinic visits will be at Screening, Randomization (Visit 2), Day 3 and Weeks 2, 4, 8, and 12, and 1 day after the Week 12 visit (Visits 1 to 8, respectively). A safety follow-up assessment will be conducted by telephone approximately 7 days after the end of the study treatment (FU Phone Contact). The total duration of subject participation, including the follow-up period will be approximately 14 weeks. All subjects will be provided with albuterol/salbutamol for use on an "as-needed" basis throughout the run-in and treatment periods.
Pre-dose spirometry will be conducted at each clinic visit. Six hour post-dose serial spirometry will be conducted at Visit 2 and at Visits 5 and 7. All subjects will be provided with a paper diary for completion everyday throughout the run-in period and 12-week treatment period. Subjects will use the diary to record their daily use of supplemental albuterol/salbutamol and to record any medical problems experienced and any medications used.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 40 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of COPD
- •10 pack-year or greater history of cigarette smoking
- •Post-bronchodilator FEV1/FVC of <0.7
- •Predicted FEV1 of 70% of normal or less
- •Modified Medical Research Council (mMRC) dyspnea score of 2 or greater
排除标准
- •Women who are pregnant, lactating, or planning to become pregnant
- •Respiratory disorders other than COPD, including a current diagnosis of asthma
- •Clinically significant non-respiratory diseases or abnormalities that are not adequately controlled
- •Significant allergy or hypersensitivity to anticholinergics, beta2-agonists, or the excipients of magnesium stereate or lactose used in the inhaler delivery device
- •Hospitalization for COPD or pneumonia within 12 weeks prior to screening
- •Lung volume reduction surgery within 12 weeks prior to screening
- •Abnormal and clinically significant ECG findings at screening
- •Clinically significant laboratory findings at screening
- •Use of systemic corticosteroids, antibiotics for respiratory tract infections, high dose inhaled steroids (>1000mcg fluticasone propionate or equivalent), PDE4 inhibitors, tiotropium, oral beta2-agoinists, short- and long-acting inhaled beta2-agonists, inhaled sodium cromoglycate or nedocromil sodium, or investigational medicines for defined time periods prior to the screening visit
- •Use of long-term oxygen therapy (12 hours or greater per day)
- •Regular use of nebulized treatment with short-acting bronchodilators
- •Participation in the acute phase of a pulmonary rehabilitation program
- •A know or suspected history of alcohol or drug abuse
- •Affiliation with the investigational site
- •Previous use of GSK573719 or the combination of GSK573719/GW642444
研究组 & 干预措施
GSK573719
active drug
干预措施: GSK573719 (Drug)
Placebo
no active drug
干预措施: Placebo (Other)
结局指标
主要结局
Change From Baseline (BL) in Trough Forced Expiratory Volume in One Second (FEV1) on Day 85
时间窗: Baseline and Day 85
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, 14, 28, 56, 84, and 85. 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 85 is the mean of the FEV1 values obtained 23 and 24 hours after the morning dosing on Day 84). Change from Baseline was calculated as the trough FEV1 minus the 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.
次要结局
- Change From Baseline in Weighted Mean (WM) 0-6 Hour FEV1 Obtained Post-dose at Days 1, 28 (Week 4) and 84 (Week 12)(Baseline and Days 1, 28 and 84)
- Change From Baseline in Serial FEV1 Over 24 Hours Post-dose at Days 1 and 84 (Week 12)(Baseline, Day 1 and Day 84)