A Multi-center, Randomized, Double-blind, Dose-ranging Study to Evaluate GSK573719 in Combination With Fluticasone Furoate, Fluticasone Furoate Alone, and an Active Control of Fluticasone Furoate/Vilanterol Combination in Subjects With Asthma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 421
- 试验地点
- 1
- 主要终点
- Percentage of Chance That FF 100 mcg Alone Corrected Change From Baseline FEV1 Response Would Exceed a Target Response by Dose of UMEC Combined With FF 100 mcg
研究概览
简要总结
Brief Summary: The purpose of this study is to characterize the dose response of GSK573719 in combination with Fluticasone furoate 100mcg in patients with asthma. Treatment with inhaled Fluticasone furoate and Fluticasone furoate/Vilanterol are included as an active control.
Detailed Description: Long acting muscarinic receptor antagonists (anti-cholinergic bronhcodilator) exert their effects via distinct and complementary bronchodilator mechanisms on large and small airways. Most of the experience with older anti-cholinergics had been with acute use and little is known about their effect in chronic use in asthma. This is a multicenter, randomized, double-blind, crossover study to evaluate 5 doses of inhaled GSK573719 inhaled over 14 days in patients with asthma. Fluticasone furoate (100 mcg) and Fluticasone furoate/Vilanterol (100/59mcg) will be included as an active comparator. Each eligible subject will receive a sequence of 3 of 7 potential treatments for a total of 3 treatment periods per subject. The total duration of subject participation is approximately 14 weeks.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Diagnostic
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Outpatient
- •18 years of age or older at Visit 1
- •Diagnosis of Asthma
- •Male or eligible Female
- •Pre-bronchodilator FEV1 of 40-80% of the predicted normal value at Visit 1
- •Demonstrated reversibility by ≥12% and ≥200mL of FEV1 within 40 minutes following albuterol at Visit 1
- •A need for regular controller therapy (i.e., inhaled corticosteroids alone or in combination with a long-acting beta-agonist, or leukotriene modifier etc.,) for a minimum of 8 weeks prior to Visit 1.
排除标准
- •History of Life threatening asthma
- •Respiratory infection not resolved
- •Asthma exacerbation
- •Concurrent respiratory disease
- •Current Smokers
- •Other diseases that are uncontrolled disease or disease state that, in the opinion of the investigator, would put the safety of the patient at risk through study participation or would confound the interpretation of the efficacy results if the condition/disease exacerbated during the study
- •A positive Hepatitis B surface antigen or positive Hepatitis C antibody and/or HIV
- •Visual clinical evidence of oropharyngeal candidiasis
- •Drug or milk protein allergies
- •Concomitant medications affecting course of asthma
- •Use of any other investigational medication within 30 days or 5 drug half-lives (whichever is longer)
- •Previous use of GSK573719
- •Any disease preventing use of anticholinergics
- •Any condition that impairs compliance with study protocol including visit schedule and completion of daily diaries
- •Any subject with a history of alcohol or substance abuse
- •Any affiliation with Investigator's site
研究组 & 干预措施
Fluticasone Furoate (FF)
100mcg, inhaled
干预措施: FF (Drug)
Fluticasone Furoate /Vilanterol (VI)
100/25mcg inhaled
干预措施: FF/VI (Drug)
Fluticasone Furoate/GSK573719
100/15.6-250mcg inhaled
干预措施: FF/GSK573719 (Drug)
结局指标
主要结局
Percentage of Chance That FF 100 mcg Alone Corrected Change From Baseline FEV1 Response Would Exceed a Target Response by Dose of UMEC Combined With FF 100 mcg
时间窗: Baseline (Day 1) and Day 15 of each treatment period
FEV1 is a lung function measure defined as the maximal amount of air that can be forcefully exhaled in one second. Highest FEV1 from the 3 acceptable spirometric efforts were recorded between 5.00 AM and 11.00 AM after withholding albuterol (salbutamol) at all visits for at least 4 hours. Baseline was defined as the pre- dose FEV1 value obtained on Day 1 and trough was defined as FEV1 value obtained 24 hours after morning dosing on Day 14 of each treatment period. Change from baseline value for each participant in each treatment period was the difference between the observed on-treatment value obtained 24 hours after morning dosing on Day 14 and the baseline value for that period. Data is presented as percentage chance that FF 100 mcg alone corrected change from baseline trough FEV1 response would exceed a target response of 50 mL, 75 mL, 100 mL and 150 mL by doses of UMEC combined with FF 100 mcg.
Model Predicted Change From Baseline Trough Force Expiratory Volume in 1 Second (FEV1)
时间窗: Baseline (Day 1) and Day 15 of each treatment period
FEV1 is a lung function measure defined as the maximal amount of air that can be forcefully exhaled in one second. Highest FEV1 from the 3 acceptable spirometric efforts were recorded between 5.00 ante meridiem (AM) and 11.00 AM after withholding albuterol (salbutamol) at all visits for at least 4 hours. Baseline was defined as the pre- dose FEV1 value obtained on Day 1 and trough was defined as FEV1 value obtained 24 hours after morning dosing on Day 14 of each treatment period. Change from baseline value for each participant in each treatment period was the difference between the observed on-treatment value obtained 24 hours after morning dosing on Day 14 and the baseline value for that period. Slope-intercept on log dose model was used to predict trough FEV1 change from baseline for each of the FF+UMEC doses adjusted by FF 100 mcg alone. Mean value for the expected response and associated 95% confidence interval (CI) in change from baseline trough FEV1 is presented.
Mean Change From Baseline in Trough FEV1 on Day 15 of Each of the 3 Treatment Periods
时间窗: Baseline (Day 1) and Day 15 of each treatment period
FEV1 is a lung function measure defined as the maximal amount of air that can be forcefully exhaled in one second. The highest FEV1 from the 3 acceptable spirometric efforts were recorded between 5.00 AM and 11.00 AM after withholding albuterol (salbutamol) at all visits for at least 4 hours. Baseline was defined as the pre- dose FEV1 value obtained on Day 1 and trough was defined as the FEV1 value obtained 24 hours after morning dosing on Day 14 of each treatment period. The change from baseline value for each participant in each treatment period was the difference between the observed on-treatment value obtained 24 hours after morning dosing on Day 14 and the baseline value for that period. Analysis was done using a mixed model, including treatment, period, period baseline FEV1, and mean baseline FEV1 as fixed effects and participant as a random effect. A post hoc analysis was performed to confirm nullification of carry over effect of UMEC.
次要结局
- Mean Change From Baseline in Daily Morning (Pre-dose and Pre-rescue Bronchodilator) Peak Expiratory Flow (PEF) of Each Treatment Period(Baseline (Week 0) and last 7 days of each treatment period)
- Mean Change From Baseline in Daily Evening (Pre-dose and Pre-rescue Bronchodilator) PEF of Each Treatment Period(Baseline (Week 0) and last 7 days of each treatment period)
- Mean Change From Baseline in Rescue Albuterol/Salbutamol Use of Each Treatment Period.(Baseline (Week 0) and last 7 days of each treatment period)