Study to Investigate the Dose Response, Safety and Efficacy of Nebulized EP-101(SUN101) in Patients With Chronic Obstructive Pulmonary Disease (COPD): GOLDEN-1 Study
A Randomized, Double-Blind, Placebo-Controlled, Multi-Center, Seven Arm, Four-Period Cross-over, Incomplete Block Design, 7-Day Dosing Study to Assess the Dose-Response, Safety, and Efficacy of EP-101 (SUN101) in Subjects With Moderate to Severe COPD
研究概览
地位
条件
详细说明
This is a phase 2, multicenter, randomized, double-blind, placebo-controlled, four-period, incomplete block design cross-over study using EP-101(SUN101) and open-label active controls (tiotropium bromide and ipratropium bromide). The study population will consist of subjects of 40-75 years of age with moderate to severe COPD. Approximately 133 subjects diagnosed with moderate to severe COPD will be enrolled in order to achieve minimum 105 subjects completing the study.
Following a run-in phase, each subject will be randomly assigned to one of 7 treatment sequences,(96 sequences when order of administration is considered), with each sequence comprised of four 7-day Treatment Periods. There will be a washout period of 7 days between each Treatment Period. Study visits will be conducted on Days 1 and 7 of each Treatment Period, with an overnight stay required in the clinic during these visits. A Final Study Visit will be conducted 7 days following the last study treatment.
During each Treatment Period, study treatments will be administered once daily (QD), except for ipratropium inhalation solution, which will be administered three times daily (TID). EP-101 (SUN101)active and placebo treatments will be administered using an investigational high-efficiency eFlow® nebulizer. Tiotropium bromide (Spiriva®) will be administered in an open-label manner via Handihaler® dry-powder inhaler (DPI). Ipratropium bromide inhalation solution will be administered in an open-label manner via general purpose nebulizer.
This study was previously posted by Elevation Pharmaceuticals, Inc. On September 5, 2012, Elevation was acquired by merger with Sunovion Pharmaceuticals Inc. ("Sunovion"), which resulted in Elevation becoming a direct wholly-owned subsidiary of Sunovion. In conjunction with this acquisition, the name of Elevation has been changed to Sunovion Respiratory Development Inc.
研究类型
注册 (实际的)
阶段
- 阶段2
联系人和位置
学习地点
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Arizona
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Phoenix、Arizona、美国、85006
- Elevation Investigational Site
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California
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Los Angeles、California、美国、90048
- Elevation Investigational Site
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Florida
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DeLand、Florida、美国、32720
- Elevation Investigational Site
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Kentucky
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Madisonville、Kentucky、美国、42431
- Elevation Investigational Site
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Massachusetts
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North Dartmouth、Massachusetts、美国、02747
- Elevation Investigational Site
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North Carolina
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Charlotte、North Carolina、美国、28207
- Elevation Investigational Site
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Raleigh、North Carolina、美国、27607
- Elevation Investigational Site
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Oregon
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Medford、Oregon、美国、97504
- Elevation Investigational Site
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South Carolina
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Spartanburg、South Carolina、美国、29303
- Elevation Investigational Site
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Washington
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Tacoma、Washington、美国、98418
- Elevation Investigational Site
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Manchester、英国、M21 8AD
- Elevation Investigational Site
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参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
Inclusion Criteria:
- 40-75 years of age
- Clinical diagnosis of moderate to severe COPD
- Current/ex-smokers with at least 10 pack-year smoking history
- Post-bronchodilator FEV1 ≥ 30% and ≤ 70% predicted normal values
- Post-bronchodilator FEV1/FVC ratio of ≤ 0.70
- Post-bronchodilator improvement in FEV1 ≥ 12% and ≤ 30%, and a minimum of 100 mL
- Willing and able to remain at the study site for at least 24 hours at each study visit
- Signed written informed consent
Exclusion Criteria:
- Current evidence or recent history of any clinically significant and unstable disease or abnormality (e.g., myocardial infarction, cardiac failure, uncontrolled hypertension, life-threatening arrhythmias, uncontrolled diabetes)
- Primary diagnosis of asthma
- History of malignancy within the past 5 years
- History of COPD exacerbation within 6 weeks of Screening
- Daily oxygen therapy > 10 hours per day
- Systemic steroids use within 6 weeks of Screening
- Respiratory tract infection within 6 weeks of Screening
- History of tuberculosis, bronchiectasis
- History of urinary retention or bladder neck obstruction type symptoms
- History of glaucoma
- Prolonged QTc interval (>460msec) or history of long QT syndrome
- Recent history of alcohol or drug abuse
- Females who are pregnant or breastfeeding, or if of child-bearing potential unwilling to practice acceptable birth control methods
- History of hypersensitivity or intolerance to aerosol medications
- Participation in another investigational drug study within 30 days of Screening
学习计划
研究是如何设计的？
设计细节
- 主要用途：治疗
- 分配：随机化
- 介入模型：交叉作业
- 屏蔽：四人间
武器和干预
参与者组/臂 |
干预/治疗 |
|---|---|
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实验性的：EP-101 via nebulizer (eFlow®) 25 ug
EP-101 via nebulizer (eFlow®)
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EP-101 (25 ug ) Dose 1 administered once daily for 7 days
其他名称：
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有源比较器：Tiotropium bromide via (Spiriva® Handihaler®)
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Tiotropium 18 µg administered once daily for 7 days using Handihaler® DPI
其他名称：
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有源比较器：Ipratropium bromide Inhalation Solution
Ipratropium bromide Inhalation Solution via Handihaler® DPI
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Ipratropium 500 µg administered three times daily for 7 days using general purpose nebulizer
其他名称：
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安慰剂比较：Placebo EP-101
Placebo
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Placebo EP-101 administered once daily for 7 days
其他名称：
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实验性的：EP-101 via nebulizer (eFlow®) 50 ug
EP-101 via nebulizer (eFlow®)
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EP-101 (50 ug ) administered once daily for 7 days
其他名称：
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实验性的：EP-101 via nebulizer (eFlow®) 100 ug
EP-101 via nebulizer (eFlow®)
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EP-101 (100ug) administered once daily for 7 days
其他名称：
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实验性的：EP-101 via nebulizer (eFlow®) 200 ug
EP-101 via nebulizer (eFlow®)
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EP-101 (200) ug administered once daily for 7 days
其他名称：
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研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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Mean Change in 24 Post Dose Trough Forced Expiratory Volume in 1 Second (FEV1)
大体时间：Day 1 and Day 7
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Spirometry measurements were conducted in accordance with the current ATS/ERS 2005 guidelines.
Trough FEV1 was defined as the mean of the spirometry values collected at 23 hours 30 minutes and 24 hours post dose for Day 1 and Day 7 within each Treatment Period.
Baseline was calculated as the mean of the FEV1 values at 45 minutes and 15 minutes prior to the morning dose at Day 1 of each Treatment Period.
Change from baseline was calculated as the trough FEV1 value minus the baseline for Day 1 and Day 7.
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Day 1 and Day 7
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Standardized Change in FEV1 Area Under the Curve (AUC) (0-12hr , 12-24hr, 0-24hr) on Day 1 and Day 7
大体时间：Day 1 and Day 7
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Spirometry measurements were conducted in accordance with the current ATS/ERS 2005 guidelines.
The standardized FEV1 AUC(0-12hr and 12-24hr) on Day 1 and Day 7 was calculated using the trapezoidal rule from the changes in FEV1 at Day 1 and Day 7, respectively, from the baseline value (the mean of the two FEV1 values at 45 minutes and 15 minutes prior to morning dose at Day 1 of the respective Treatment Periods) and dividing by the actual length of the time interval.
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Day 1 and Day 7
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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Peak FEV1 (Maximum FEV1 During the First 4 Hours Post-dose on Day 1 and Day 7)
大体时间：Day 1 and Day 7
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Spirometry measurements were conducted in accordance with the current ATS/ERS 2005 guidelines
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Day 1 and Day 7
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Treatment Responders (Number of Subjects With Clinically Meaningful Change From Pre-dose in Trough FEV1 on Day 1 and Day 7)
大体时间：Day 1 and Day 7
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Spirometry measurements were conducted in accordance with the current ATS/ERS 2005 guidelines.
Clinically meaningful is defined as when the change from baseline (mean of the two pre-dose values at Day 1) in 24 hour trough FEV1 on a SUN-101 treatment is more than 100 mL compared to the mean change in trough FEV1 from all subjects on the placebo treatment.
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Day 1 and Day 7
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Number of Participants With Adverse Events, Vital Signs, and Clinically Significant Abnormal ECG Values and Laboratory Tests
大体时间：Day 1 through Day 7
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AEs are defined as existing conditions which worsen or events which occur during the course of the clinical trial after treatment.
Vital signs were performed during the screening period to confirm study eligibility and at the final study visit.
ECGs were performed during the screening period to confirm study eligibility.
Vital signs and ECG were additionally collected within 30 minutes pre-dose; and 30 minutes, and 1, 2, 4, 6, 12 hours, and 23 hours 45 minutes post-dose within each treatment period.
Clinical laboratory assessments were conducted during the screening period, at each study visit during each treatment period, and at the final study visit.
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Day 1 through Day 7
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Rescue Medication Use
大体时间：Day 1 through Day 7
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Mean number of puffs of daily rescue medication
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Day 1 through Day 7
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Treatment Responders (Percentage of Subjects With Clinically Meaningful Change From Pre-dose in Trough FEV1 on Day 1 and Day 7)
大体时间：Day 1 and Day 7
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percentage of subjects with clinically meaningful change from pre-dose in trough FEV1 on Day 1 and Day 7 Spirometry measurements were conducted in accordance with the current ATS/ERS 2005 guidelines.
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Day 1 and Day 7
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合作者和调查者
调查人员
- 研究主任：Ahmet Tutuncu, M.D., Ph.D.、Chief Medical Officer / Elevation Pharmaceuticals, Inc.
研究记录日期
研究主要日期
学习开始
初级完成 (实际的)
研究完成 (实际的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (估计)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
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