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
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 140
- 试验地点
- 2
- 主要终点
- Mean Change in 24 Post Dose Trough Forced Expiratory Volume in 1 Second (FEV1)
研究概览
简要总结
The purpose of this study is to determine steady-state efficacy and dose response profile and to assess safety and pharmacokinetic profile of nebulized EP-101(SUN101) after 7-day dosing using an investigational high efficiency nebulizer (eFlow®) compared with placebo and two active comparators in patients with moderate to severe Chronic Obstructive Pulmonary Disease (COPD).
详细描述
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
EP-101 via nebulizer (eFlow®) 25 ug
EP-101 via nebulizer (eFlow®)
干预措施: EP-101 via nebulizer (eFlow®) 25 ug (Drug)
Tiotropium bromide via (Spiriva® Handihaler®)
Tiotropium bromide via (Spiriva® Handihaler®)
干预措施: Tiotropium bromide via (Spiriva® Handihaler®) (Drug)
Ipratropium bromide Inhalation Solution
Ipratropium bromide Inhalation Solution via Handihaler® DPI
干预措施: Ipratropium bromide Inhalation Solution via Handihaler® DPI (Drug)
Placebo EP-101
Placebo
干预措施: Placebo EP-101 (Drug)
EP-101 via nebulizer (eFlow®) 50 ug
EP-101 via nebulizer (eFlow®)
干预措施: EP-101 via nebulizer (eFlow®) 50 ug (Drug)
EP-101 via nebulizer (eFlow®) 100 ug
EP-101 via nebulizer (eFlow®)
干预措施: EP-101 via nebulizer (eFlow®) 100 ug (Drug)
EP-101 via nebulizer (eFlow®) 200 ug
EP-101 via nebulizer (eFlow®)
干预措施: EP-101 via nebulizer (eFlow®) 200 ug (Drug)
结局指标
主要结局
Mean Change in 24 Post Dose Trough Forced Expiratory Volume in 1 Second (FEV1)
时间窗: Day 1 and Day 7
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.
Standardized Change in FEV1 Area Under the Curve (AUC) (0-12hr , 12-24hr, 0-24hr) on Day 1 and Day 7
时间窗: Day 1 and Day 7
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.
次要结局
- Peak FEV1 (Maximum FEV1 During the First 4 Hours Post-dose on Day 1 and Day 7)(Day 1 and Day 7)
- Treatment Responders (Number of Subjects With Clinically Meaningful Change From Pre-dose in Trough FEV1 on Day 1 and Day 7)(Day 1 and Day 7)
- Number of Participants With Adverse Events, Vital Signs, and Clinically Significant Abnormal ECG Values and Laboratory Tests(Day 1 through Day 7)
- Rescue Medication Use(Day 1 through Day 7)
- Treatment Responders (Percentage of Subjects With Clinically Meaningful Change From Pre-dose in Trough FEV1 on Day 1 and Day 7)(Day 1 and Day 7)