A Randomized, Double-Blind, 3-Way, Cross-Over Study to Evaluate Lung Function Response After Treatment With Umeclidinium 62.5mcg, Vilanterol 25mcg, and Umeclidinium/Vilanterol 62.5/25mcg Once-Daily in Subjects With Chronic Obstructive Pulmonary Disease (COPD)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 182
- 试验地点
- 22
- 主要终点
- Change From Baseline (BL) in Weighted Mean (WM) 0-6 Hour Forced Expiratory Volume in One Second (FEV1) Obtained Post-dose at Day 14 of Each Treatment Period (TP) by Response Type
研究概览
简要总结
The purpose of this study is to evaluate the lung function response to UMEC/VI, UMEC, and VI in individual patients using a cross-over design. This is a multicenter, randomized, double-blind, 3-way crossover study. Eligible subjects will be randomized to a sequence of UMEC 62.5mcg, VI 25mcg, and UMEC/VI 62.5/25mcg. All subjects will receive each treatment once-daily for 14 days, and each treatment will be separated by a 10-14 day washout period. There will be a 5-7 day run-in period prior to randomization.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Type of Patient: Outpatient
- •Informed Consent: A signed and dated written informed consent prior to study participation
- •Age: Subjects 40 years of age or older at Visit 1
- •Gender: Male or female subjects.
- •COPD diagnosis: As defined by the American Thoracic Society/European Respiratory Society (ATS/ERS)
- •Severity of disease: A pre- and post-salbutamol FEV1/FVC ratio of <0.70 and a pre- and post-salbutamol FEV1 of ≤ 70% of predicted normal values at Visit 1
- •Smoking History: Current or former cigarette smokers with a history of cigarette smoking of ≥ 10 pack-years at Visit 1
- •Female subject of non child-bearing potential OR a female subject of child bearing potential, with a negative pregnancy test at screening, and agreeing to consistently and correctly use one of the acceptable contraceptive methods
排除标准
- •Pregnancy: Women who are pregnant or lactating or are planning on becoming pregnant during the study
- •Asthma: A current diagnosis of asthma
- •Other Respiratory Disorders: Known alpha-1 antitrypsin deficiency, active lung infections (such as tuberculosis), and lung cancer are absolute exclusionary conditions.
- •Other Diseases/Abnormalities: Subjects with historical or current evidence of clinically significant cardiovascular, neurological, psychiatric, renal, hepatic, immunological, endocrine (including uncontrolled diabetes or thyroid disease) or hematological abnormalities that are uncontrolled and/or a previous history of cancer in remission for < 5 years prior to Visit 1
- •Contraindications: A history of allergy or hypersensitivity to any anticholinergic/muscarinic receptor antagonist, beta2-agonist, lactose/milk protein or magnesium stearate or a medical condition such as of narrow-angle glaucoma, prostatic hypertrophy or bladder neck obstruction that, in the opinion of the study physician contraindicates study participation or use of an inhaled anticholinergic.
- •Hospitalization: Hospitalization for COPD or pneumonia within 12 weeks prior to Visit
- •Lung Resection: Subjects with lung volume reduction surgery within the 12 months prior to Visit
- •12-Lead ECG: An abnormal and significant ECG finding from the 12-lead ECG conducted at Visit 1
- •Screening Labs: Significantly abnormal finding from clinical chemistry or hematology tests at Visit 1 as determined by the study investigator.
- •Medication Prior to Spirometry: Unable to withhold salbutamol for the 4 hour period required prior to spirometry testing at each study visit and at each spirometry test performed at home.
- •Medications Prior to Screening: Use of the prohibited medications according to defined time intervals prior to Visit 1
- •Oxygen: Use of long-term oxygen therapy (LTOT) described as oxygen therapy prescribed for greater than 12 hours a day. As-needed oxygen use (i.e., ≤ 12 hours per day) is not exclusionary.
- •Nebulized Therapy: Regular use (prescribed for use every day, not for as-needed use) of short-acting bronchodilators (e.g., salbutamol, ipratropium bromide) via nebulized therapy
- •Pulmonary Rehabilitation Program: Participation in the acute phase of a pulmonary rehabilitation program within 4 weeks prior to Visit
- •Subjects who are in the maintenance phase of a pulmonary rehabilitation program are not excluded.
- •Drug or Alcohol Abuse: A known or suspected history of alcohol or drug abuse within 2 years prior to Visit
- •Affiliation with Investigator Site: Is an investigator, sub-investigator, study coordinator, employee of a participating investigator or study site, or immediate family member of the aforementioned that is involved in this study.
- •Inability to read: In the opinion of the Investigator, any subject who is unable to read and/or would not be able to complete a questionnaire
结局指标
主要结局
Change From Baseline (BL) in Weighted Mean (WM) 0-6 Hour Forced Expiratory Volume in One Second (FEV1) Obtained Post-dose at Day 14 of Each Treatment Period (TP) by Response Type
时间窗: Baseline and Day 14 of each treatment period (up to study day 83)
FEV1 is a measure of lung function and the maximal amount of air that can be forcefully exhaled in one second. The WM FEV1 was derived by calculating the area under the FEV1/time curve (AUC) using the trapezoidal rule, and then dividing the value by the time interval over which the AUC was calculated. The WM FEV1 was calculated using 0-6 hour post-dose measurements at Day 14 of each TP, which included pre-dose (trough value for Day 14 \[mean of the 23 and 24 hour assessments post Day 13 dosing\]) and post-dose 15 minutes (min), 30 min, and 1, 3, and 6 hours. BL is the mean FEV1 values recorded 30 min and 5 min pre-dose on Day 1 of each TP, mean BL is the mean of the BLs for each participant, and period BL is the difference between the BL and the mean BL in each TP for each participant. Change from BL for each TP is the Day 14 value minus the BL value for that TP. Participants could have been classified as responders to both UMEC and VI.
次要结局
- Number of Participants (Par.) Who Were Responsive to UMEC/VI, UMEC, or VI According to FEV1 at Day 1 of Each Treatment Period (TP)(Baseline (BL) and 0-6 hours post-dose (15 minutes, 30 minutes, and 1, 3, and 6 hours post-dose) on Day 1 of each treatment period (up to study day 71))
- Number of Participants With a Larger Change From Baseline in 0-6 Hour Weighted Mean FEV1 at Day 14 of Each Treatment Period With UMEC/VI Compared With UMEC and VI Alone(Baseline and Day 14 of each treatment period (up to study day 83))
- Change From Baseline in Trough FEV1 on Day 15 of Each Treatment Period(Baseline and Day 15 of each treatment period (up to study day 84))