A Randomised, Double-Blind, Placebo-Controlled, Parallel-Group, Multi-centre, Dose Ranging Study to Evaluate the Efficacy and Safety of Losmapimod (GW856553) Tablets Administered Twice Daily Compared With Placebo for 24 Weeks in Adult Subjects With Chronic Obstructive Pulmonary Disease
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 604
- 试验地点
- 1
- 主要终点
- Change From Baseline in Six Minute Walk Distance (6MWD) at Week 4, 12 and 24
研究概览
简要总结
Randomised, double-blind, parallel-group, multi-centre study evaluating three doses of losmapimod (2.5mg, 7.5 mg and 15 mg) twice daily (BID) versus placebo on exercise tolerance. Eligible subjects will be randomised to treatment after a one-week run-in period. The duration of the treatment period is 24 weeks. An estimated 1000 subjects will be screened to reach the target enrolment of approximately 600 randomised subjects.
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
- •clinical history of COPD in accordance with the definition by the American Thoracic Society/European Respiratory Society
- •FEV1/FVC ratio of ≤0.70
- •FEV1 ≤ 80% of predicted normal
- •6MWD < 350m
- •male or female outpatients aged ≥40 years of age
- •current or prior history of ≥10 pack-years of cigarette smoking
- •aspartate transaminase (AST) or alanine transaminase (ALT) <2x Upper Limit Normal (ULN)
- •alkaline phosphatase (alk phos), and bilirubin <1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%)
- •QTc <450 msec* on baseline ECG. For subjects with baseline complete bundle branch block, the QTc must be <480msec* on baseline ECG.
排除标准
- •current diagnosis of asthma
- •pregnant or lactating
- •α1-antitrypsin deficiency
- •lung resection
- •chest X-ray (or CT scan) that reveals evidence of clinically significant abnormalities not believed to be due to the presence of COPD
- •exacerbation of COPD within previous 12 weeks
- •treatment with roflumilast within previous 2 weeks and throughout the treatment period
- •lower respiratory tract infection that required the use of antibiotics within previous 12 weeks
- •long-term oxygen therapy (LTOT) or nocturnal oxygen therapy required for greater than 12 hours a day
- •participation in the acute phase of a Pulmonary Rehabilitation Program within 12 weeks or planned during the study
- •carcinoma that has not been in complete remission for at least 5 years
- •current or chronic history of liver disease
- •positive Hepatitis B surface antigen or positive Hepatitis C antibody
- •Body Mass Index (BMI) > 35
- •known or suspected history of alcohol or drug abuse within the last 2 years
研究组 & 干预措施
losmapimod 2.5 mg
losmapimod 2.5 mg
干预措施: losmapimod (Drug)
placebo
干预措施: placebo (Drug)
losmapimod 7.5 mg
losmapimod 7.5 mg
干预措施: losmapimod (Drug)
losmapimod 15 mg
losmapimod 15 mg
干预措施: losmapimod (Drug)
结局指标
主要结局
Change From Baseline in Six Minute Walk Distance (6MWD) at Week 4, 12 and 24
时间窗: Baseline (Week 0) and Week 4, 12, 24
Exercise tolerance was assessed using the 6MWD. If a participant was recorded as having used supplemental oxygen or a walking aid (including sitting down then continuing walking) or a technical problem during a 6MWD then that walk was considered as invalid; otherwise the 6MWD was considered as valid. The baseline 6MWD value was defined as the longest distance walked, for a valid walk, at Visit 2. Variability between the distances walked during the first six-minute walk test (6MWD1) and the second six-minute walk test (6MWD2) being compared was defined as: Variability = \[100 x (6MWD2 - 6MWD1)\]/6MWD1. Change from Baseline was calculated as the endpoint value minus the Baseline value. Baseline visit was Visit 2 (Week 0).
次要结局
- Change From Baseline in Forced Vital Capacity (FVC) at Week 4, 8, 12, 16, 20 and 24(Baseline(Week 0) and Week 4, 8, 12, 16, 20 and 24)
- Least Square Mean Ratio to Baseline of Plasma Fibrinogen Over 24 Weeks(Baseline (Week 0) and Week 4, 8, 12, 24)
- Change From Baseline in Forced Expiratory Volume in 1 Sec (FEV1) at Week 4, 8, 12, 16, 20 and 24(Baseline(Week 0) and Week 4, 8, 12, 16, 20 and 24)
- Least Square Mean Ratio to Baseline of High Sensitivity C-reactive Protein (HsCRP) Over 24 Weeks(Baseline (Week 0) and Week 4, 8, 12, 24)
- Total Number of Exacerbations Over 24 Weeks(Up to 24 weeks)
- Change From Baseline in St Georges Respiratory Questionnaire for COPD (SGRQ-C) at Week 12 and 24(Baseline (Week 0) and Week 12, 24)
- Change From Baseline in Inspiratory Capacity (IC), Residual Volume(RV), Total Lung Capacity(TLC) , Thoracic Gas Volume (TGV) at Functional Residual Capacity ( FRC), Slow Vital Capacity (SVC) at Week 12 and 24(Baseline(Week 0) and Week 12, 24)