A 52 Week Study to Evaluate the Safety and Tolerability of GSK573719/GW642444 125mcg Once-daily Alone and in Combination With GW642444 25mcg Once-daily Via Novel Dry Powder Inhaler (nDPI) in Subjects With Chronic Obstructive Pulmonary Disease
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 563
- 试验地点
- 1
- 主要终点
- Number of Participants With Any On-treatment Adverse Event (AE) or Any Serious Adverse Event (SAE)
研究概览
简要总结
The purpose of this 52-week study is to evaluate the long-term safety (in terms of adverse events, COPD exacerbations, laboratory, ECG, and Holter findings, vital signs, use of rescue medication and lung function) of GSK573719/GW642444 Inhalation Powder 125/25mcg in subjects with COPD. The long-term safety of GSK573719 Inhalation Powder 125mcg will also be evaluated. A placebo arm is included to evaluate these products compared to an inactive control.
详细描述
Several studies have demonstrated the efficacy and safety of combining an individual LABA compound plus an individual LAMA compound in COPD. These studies have shown the combination of these two products to be superior to either agent alone on a variety of outcomes in COPD. The beneficial effects of this combination regimen are likely due to the different mechanisms of action of the two bronchodilators (smooth bronchial muscle relaxation from activation of beta2 receptors from the LABA product and inhibition of acetylcholine-mediated smooth bronchial muscle contraction via blockade of muscarinic receptors from the LAMA product). The availability of a LABA/LAMA combination in one product instead of two individual products is a technical and therapeutic advancement in the pharmacological armamentarium for COPD and may lead to increased patient compliance due to once-daily administration. The purpose of this 52-week study is to evaluate the long-term safety (in terms of adverse events, COPD exacerbations, laboratory, ECG, and Holter findings, vital signs, use of rescue medication, and lung function) of GSK573719/GW642444 Inhalation Powder 125/25mcg in subjects with COPD. The long-term safety of GSK573719 Inhalation Powder 125mcg will also be evaluated. A placebo arm is included to evaluate these products compared to an inactive control. All treatments will be delivered once-daily via the nDPI. This study will establish the long-term safety profile of GSK573719/GW642444 Inhalation Powder 125/25mcg once-daily in subjects with COPD. The safety profile of GSK573719 Inhalation Powder125mcg once-daily will also be evaluated.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 40 Years 至 120 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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 greater than or equal to 35% and less than or equal to 80% of predicted normal
排除标准
- •Pregant or lactating women or women planning to become 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
- •abnormal and clinically significant Holter monitor finding at Visit 1
- •significantly abnormal finding from laboratory tests at Visit 1
- •unable to withhold albuterol/salbutamol and/or ipratropium bromide 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 within 6 weeks of Visit 1
- •use of anitbiotics for lower respiratory tract infection within 6 weeks of Visit 1
- •use of cytochrome P450 3A4 inhibitors within 6 weeks of Visit 1
- •us of long-acting beta-agonist (LABA)/inhaled corticosteroid (ICS) products if LABA/ICS therapy is discontinued completely within 30 days of Visit 1
- •use of ICS at a dose of >10000mcg/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 within 14 days of Visit 1
- •use of roflumilast within 14 days of Visit 1
- •use of theophyllines within 48 hours of Visit 1
- •use of oral leukotriene inhibitors within 48 hours prior to Visit 1
- •use of long-acting oral beta-agonists within 48 hours of Visit 1
- •use of short-acting oral beta-agonists within 12 hours of Visit 1
- •use of inhaled long-acting beta-agonists within 48 hours prior to 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 within 4 hours of Visit 1
- •use of inhaled short-acting anticholinergics within 4 hours of Visit 1
- •use of inhaled short-acting anticholinergic/short-acting beta2-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) of Visit 1
- •long-term oxygen therapy prescribed for >12 hours per day
- •regular use of short-acting bronchodilators
- •use of CPAP or NIPPV
- •participation in the maintenance phase of a pulmonary rehabilitation program
- •known or suspected history of alcohol or drug abluse with 2 years prior to Visit 1
- •anyone affiliated with the investigator site (e.g., investigator, study coordinator, etc.)
- •previous use of GSK573719, GW642444 , GSK573719/GW642444 combination, GSK233705/GW642444 combination, or Fluticasone Furoate/GW642444 combination
研究组 & 干预措施
GSK573719/GW642444
125/25 mcg once-daily
干预措施: 125/25 mcg once-daily GSK573719/GW642444 (Drug)
GSK573719
125 mcg once-daily
干预措施: 125mcg once-daily GSK573719 (Drug)
Placebo
inactive
干预措施: Placebo once-daily (Drug)
结局指标
主要结局
Number of Participants With Any On-treatment Adverse Event (AE) or Any Serious Adverse Event (SAE)
时间窗: From the start of study drug up to 52 weeks
An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, or is an event of possible drug-induced liver injury with hyperbilirubinaemia. Medical or scientific judgment was to have been exercised in other important medical events. AEs with an onset on or after the date of the first dose of study drug and up to 1 day after the date of the last recorded dose of study drug were considered to be on-treatment AEs, Refer to the general AE/SAE module for a complete list of AEs and SAEs.
次要结局
- Number of Participants With at Least One Chronic Obstructive Pulmonary Disease (COPD) Exacerbation Over the Course of the 52-week Treatment Period(From the start of study drug up to 52 weeks)
- Change From Baseline in the Percentage of Basophils, Eosinophils, Lymphocytes, Monocytes, and Segmented Neutrophils in Blood at Months 3, 6, 9, and 12(Baseline; Months 3, 6, 9, and 12)
- Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Creatine Kinase (CK), and Gamma Glutamyl Transferase (GGT) at Months 3, 6, 9, and 12(Baseline; Months 3, 6, 9, and 12)
- Change From Baseline in Albumin, Total Protein, and Hemoglobin at Months 3, 6, 9, and 12(Baseline; Months 3, 6, 9, and 12)
- Change From Baseline in Calcium, Carbon Dioxide (CO2) Content/Bicarbonate, Chloride, Glucose, Inorganic Phosphorus (IP), Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) at Months 3, 6, 9, and 12(Baseline; Months 3, 6, 9, and 12)
- Change From Baseline in Creatinine, Direct Bilirubin, Indirect Bilirubin, Total Bilirubin, and Uric Acid at Months 3, 6, 9, and 12(Baseline; Months 3, 6, 9, and 12)
- Time to the First On-treatment COPD Exacerbation(From the start of study drug up to 52 weeks)
- Change From Baseline in Eosinophil Count, Platelet Count, and White Blood Cell (WBC) Count at Months 3, 6, 9, and 12(Baseline; Months 3, 6, 9, and 12)
- Change From Baseline in Hematocrit at Months 3, 6, 9, and 12(Baseline; Months 3, 6, 9, and 12)
- Change From Baseline to Maximum Systolic Blood Pressure (SBP) and Change From Baseline to Minimum Diastolic Blood Pressure (DBP) Over the Course of the 52-week Treatment Period(Baseline; from the start of study drug up to 52 weeks)
- Maximum Change From Baseline in Pulse Rate Over the Course of the 52-week Treatment Period(Baseline; from the start of study drug up to 52 weeks)
- Maximum Change From Baseline in the Electrocardiogram (ECG) Parameters of QT Interval Corrected for Heart Rate by Bazett's Formula (QTcB), QT Interval Corrected for Heart Rate by Fridericia's Formula (QTcF), and PR Interval Over the Course of the 52-week(Baseline; from the start of study drug up to 52 weeks)
- Maximum Change From Baseline in the ECG Parameter of Heart Rate Over the Course of the 52-week Treatment Period(Baseline; from the start of study drug up to 52 weeks)
- Number of Participants With the Indicated ECG Result Interpretations at Any Time Post-Baseline(From the start of study drug up to 52 weeks)
- Number of Participants With the Indicated Change From Screening to Any Time Post-Baseline in Holter ECG Interpretation(Screening; from the start of study drug up to 52 weeks)
- Change From Baseline in the Mean Number of Puffs of Rescue Medication (Salbutamol and/or Ipratropium Bromide) Per Day Over the Course of the 52-week Treatment Period(Baseline; from the start of study drug up to 52 weeks)
- Change From Baseline in the Percentage of Rescue-free Days Over the Course of the 52-week Treatment Period(From the start of study drug up to 52 weeks)
- Change From Baseline in Trough Forced Expiratory Volume in One Second (FEV1) and Forced Vital Capacity (FVC) at Months 1, 3, 6, 9, and 12(Baseline; Months 1, 3, 6, 9, and 12)