A 24-Week, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of GSK573719/GW642444 Inhalation Powder and the Individual Components 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
- 1,493
- 试验地点
- 1
- 主要终点
- Change From Baseline (BL) in Trough Forced Expiratory Volume in One Second (FEV1) on Day 169 (Week 24)
研究概览
简要总结
This is a phase III multicenter, randomized, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy and safety of GSK573719/GW642444 Inhalation Powder, GSK573719 Inhalation Powder, GW642444 Inhalation Powder and Placebo when administered once-daily via a Novel Dry Powder Inhaler over a 24-week treatment period in subjects with COPD. Subjects who meet eligibility criteria at Screening (Visit 1) will complete a 7 to14 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 27 weeks. A subset of subjects at selected sites will also perform 24-hour serial spirometry and Holter monitoring during the study and provide serial blood samples for pharmacokinetic analysis. Sparse pharmacokinetic sampling for population pharmacokinetic analyses will be obtained from non-subset subjects. The primary measure of efficacy is clinic visit trough (pre-bronchodilator and pre-dose) FEV1 on Treatment Day 169. Safety will be assessed by adverse events, 12-lead ECGs, vital signs, clinical laboratory tests, and 24 hour Holter monitoring (subset only).
详细描述
This is a 24-week, phase III multicenter, randomized, double-blind, placebo-controlled, parallel-group study.
Eligible subjects will be randomized to GSK573719/GW642444 125/25mcg, GSK573719 125mcg, GW642444 25mcg, and placebo treatment groups in a 3:3:3:2 ratio such that of the planned 1463 total number of randomized subjects approximately 399 subjects will be randomized to each active treatment group and 266 subjects will be randomized to placebo. All treatments will be administered once-daily in the morning by inhalation using a Novel Dry Powder Inhaler (Novel DPI).
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 14 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 27 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/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, 4, 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 evening throughout the run-in and treatment periods. Subjects will use the eDiary to record 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.
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
- Quadruple (Participant, Care Provider, 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, strong cytochrome P450 3A4 inhibitors, high dose inhaled steroids (>1000mcg fluticasone propionate or equivalent), PDE4 inhibitors, tiotropium, oral beta2-agoinists, short- and long-acting inhaled beta2-agonists, ipratropium, 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 GW642444 alone or in combination, including the combination of fluticasone furoate and GW642444
研究组 & 干预措施
GSK573719/GW642444
125/25mcg
干预措施: GSK573719/GW642444 125/25mcg (Drug)
GSK573719
125mcg
干预措施: GSK573719 125mcg (Drug)
GW642444
25mcg
干预措施: GW642444 25mcg (Drug)
Placebo
Placebo
干预措施: Placebo only (Drug)
结局指标
主要结局
Change From Baseline (BL) in Trough Forced Expiratory Volume in One Second (FEV1) on Day 169 (Week 24)
时间窗: 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.
次要结局
- Mean Transition Dyspnea Index (TDI) Focal Score at Day 168 (Week 24)(Day 168 (Week 24))
- Change From Baseline in Weighted Mean (WM) 0-6 Hour FEV1 Obtained Post-dose at Day 168(Baseline and Day 168)