A Randomized, Double-Blind, Placebo-Controlled, 3-Way Cross-Over Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of GSK573719 Administered Once- and Twice-Daily in Subjects With COPD
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 176
- 试验地点
- 1
- 主要终点
- Change From Baseline in Trough Forced Expiratory Volume in One Second (FEV1) at Day 15 of Each Treatment Period
研究概览
简要总结
The study will evaluate the dose response, safety, and pharmacokinetics of GSK573719 compared with placebo in subjects with COPD.
详细描述
This is multicenter, randomized, double-blind, double-dummy, placebo-controlled, three-way cross-over, incomplete block design study to evaluation of 5 doses of GSK573719 administered once-daily and 3 doses of GSK573719 administered twice-daily over 14 days in subjects with COPD and will include tiotropium as an open-label active control. The pharmacokinetic profile of GSK573719 will also be evaluated.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 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 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •A signed and dated written informed consent prior to study participation
- •Males or females of non-childbearing potential
- •40 to 80 years of age
- •COPD diagnosis
- •10 pack-years history or greater of cigarette smoking
- •Post-bronchodilator FEV1/FVC ratio of 0.70 or less
- •Post-bronchodilator FEV1 of 35 to 70% of predicted normal
排除标准
- •Other significant respiratory disorders besides COPD, including alpha-1 deficiency
- •Previous lung resection surgery
- •Use of oral steroids or antibiotics for a COPD exacerbation within 6 weeks of screening
- •Hospitalization for COPD or pneumonia within 3 months of screening
- •Any significant disease that would put subject at risk through study participation
- •BMI greater than 35
- •Pacemaker
- •Significantly abnormal ECG, Holter, or clinical lab finding (including Hepatitis B or C)
- •Allergy or hypersensitivity to anticholinergics or inhaler excipients
- •Diseases that would contra-indicate the use of anticholinergics
- •Use of oral corticosteroids within 6 weeks of screening
- •Use of long-acting beta-agonists within 48 hours of screening
- •Use of tiotropium within 14 days of screening
- •Use of theophyllines or anti-leukotrienes within 48 hours of screening
- •Use of short-acting bronchodilators within 4 to 6 hours of screening
- •Use of investigational medicines within 30 days of screening
- •Use of high dose inhaled corticosteroids
- •Use of long-term oxygen therapy, CPAP or NIPPV
- •Previous use of GSK573719
研究组 & 干预措施
Arm 8
GSK573719 62.5mcg twice daily
干预措施: GSK573179 (Drug)
Tiotropium
Tiotropium
干预措施: Tiotropium (Drug)
Placebo
Placebo
干预措施: Placebo (Drug)
Arm 1
GSK573719 1000mcg once daily
干预措施: GSK573179 (Drug)
Arm 2
GSK573719 500mcg once daily
干预措施: GSK573179 (Drug)
Arm 3
GSK573719 250mcg once daily
干预措施: GSK573179 (Drug)
Arm 4
GSK573719 125mcg once daily
干预措施: GSK573179 (Drug)
Arm 5
GSK573719 62.5 mcg once daily
干预措施: GSK573179 (Drug)
Arm 6
GSK573719 250mcg twice daily
干预措施: GSK573179 (Drug)
Arm 7
GSK573719 125mcg twice daily
干预措施: GSK573179 (Drug)
结局指标
主要结局
Change From Baseline in Trough Forced Expiratory Volume in One Second (FEV1) at Day 15 of Each Treatment Period
时间窗: Baseline and Day 15 of each treatment period (up to Study Day 71)
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 on Treatment Day 15 is defined as the value obtained 24 hours after the morning dose administered on Day 14. Analysis were performed using a mixed model with covariates of mean Baseline, period Baseline, treatment and period as fixed effects and participant as a random effect. Baseline is the FEV1 value recorded pre-dose on Day 1 of each treatment period; mean Baseline is the mean of the Baselines for each participant and period Baseline is the difference between the Baseline and the mean Baseline in each treatment period for each participant. Change from Baseline for each treatment period is the trough FEV1 at Day 15 minus the Baseline value for that treatment period.
次要结局
- Change From Baseline (BL) in Weighted Mean FEV1 Over 0 to 24 Hours Obtained Post-dose on Day 14 of Each Treatment Period(Baseline and Day 14 of each treatment period (TP; up to Study Day 70))
- Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period(Baseline and Day (D) 14 of each treatment period (TP; up to Study Day 70))