Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Multicenter, Efficacy and Safety Trial of 12 Weeks of Treatment With Nebulized SUN-101 in Patients With COPD: GOLDEN-3 (Glycopyrrolate for Obstructive Lung Disease Via Electronic Nebulizer)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 653
- 试验地点
- 43
- 主要终点
- Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) at Week 12
研究概览
简要总结
This is a trial of 12 weeks of treatment with nebulized SUN-101 using an Investigational eFlow® Closed System (CS) nebulizer in subjects with chronic obstructive pulmonary disease (COPD) according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD 2014) guidelines.
详细描述
This is a Phase 3, randomized, double-blind, placebo-controlled, parallel-group, multicenter, efficacy and safety trial of 12 weeks of treatment with nebulized SUN-101 using an Investigational eFlow® Closed System (CS) nebulizer in approximately 645 subjects with chronic obstructive pulmonary disease (COPD) according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD 2014) guidelines.
SUN-101 or placebo will be administered twice daily as an oral inhalation using the investigational eFlow CS nebulizer. Approximately 150 subjects will be enrolled in the substudy (at selected sites only). These subjects will be required to participate in serial spirometry, vital signs, ECGs, and an additional Holter monitor assessment at Visit 6 (Week 12). This subset of subjects will be referred to as the Substudy Population.
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
- 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
- •Male or female patients age ≥ 40 years, inclusive
- •A clinical diagnosis of COPD according to the GOLD 2014 guidelines
- •Current smokers or ex-smokers with at least 10 pack-year smoking history (eg, at least 1 pack/day for 10 years, or equivalent)
- •Post-bronchodilator (following inhalation of ipratropium bromide) FEV1 < 80% of predicted normal and > 0.7 L during Screening (Visit 1)
- •Post-bronchodilator (following inhalation of ipratropium bromide) FEV1/FVC ratio < 0.70 during Screening (Visit 1)
- •Ability to perform reproducible spirometry according to the American Thoracic Society (ATS) and European Respiratory Society (ERS) guidelines (2005)
- •Subject, if female ≤ 65 years of age and of child bearing potential, must have a negative serum pregnancy test at Visit
- •Females of childbearing potential must be instructed to and agree to avoid pregnancy during the study and must use an acceptable method of birth control: a) an oral contraceptive, an intrauterine device (IUD), implantable contraceptive, transdermal or injectable contraceptive for at least 1 month prior to entering the study with continued use throughout the study and for thirty days following participation; b) barrier method of contraception, eg, condom and /or diaphragm with spermicide while participating in the study; and/or c) abstinence
- •Willing and able to provide written informed consent
- •Willing and able to attend all study visits and adhere to all study assessments and procedures
排除标准
- •Severe comorbidities including unstable cardiac or pulmonary disease or any other medical conditions that would, in the opinion of the Investigator, preclude the subject from safely completing the required tests or the study, or is likely to result in disease progression that would require withdrawal of the subject
- •Concomitant clinically significant respiratory disease other than COPD (eg, asthma, tuberculosis, bronchiectasis or other non-specific pulmonary disease).
- •Recent history of COPD exacerbation requiring hospitalization or need for increased treatments for COPD within 6 weeks prior to Screening (Visit 1)
- •Use of daily oxygen therapy > 12 hours per day
- •Respiratory tract infection within 6 weeks prior to Screening (Visit 1)
- •Use of oral, intravenous, or intramuscular steroids within 3 months prior to Screening (Visit 1)
- •History of malignancy of any organ system, treated or untreated within the past 5 years, with the exception of localized basal cell carcinoma of the skin
- •Prolonged QTcF (> 450 msec for males and > 470 msec for females) during Screening (Visit 1) as determined from the report provided by the central laboratory, or history of long QT syndrome
- •History of or clinically significant ongoing bladder outflow obstruction or history of catheterization for relief of bladder outflow obstruction within the previous 6 months.
- •History of narrow angle glaucoma
- •History of hypersensitivity or intolerance to aerosol medications
- •Recent documented history (within the previous 3 months) of substance abuse
- •Significant psychiatric disease that would likely result in the subject not being able to complete the study, in the opinion of the Investigator
- •Participation in another investigational drug study where drug was received within 30 days prior to Screening (Visit 1) or current participation in another investigational drug trial, including a SUN-101 study
- •Previously received SUN-101 (active treatment; formerly known as EP-101).
- •Contraindicated for treatment with, or having a history of reactions/hypersensitivity to anticholinergic agents, beta2 agonists, or sympathomimetic amines
研究组 & 干预措施
SUN-101 50 mcg BID eFlow (CS) nebulizer
SUN-101 50 mcg twice daily (BID) eFlow (R) Closed System (CR) nebulizer
干预措施: SUN-101 50 mcg BID eFlow (CS) nebulizer (Drug)
SUN-101 25 mcg BID eFlow (CS) nebulizer
SUN-101 25 mcg twice daily (BID) eFlow (R) Closed System (CR) nebulizer
干预措施: SUN-101 25 mcg BID eFlow (CS) nebulizer (Drug)
Placebo BID eFlow (CS) nebulizer
Placebo twice daily (BID) eFlow (R) Closed System (CR) nebulizer
干预措施: Placebo BID eFlow Closed System (CS) nebulizer (Drug)
结局指标
主要结局
Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) at Week 12
时间窗: Baseline and Week 12
ALL COLLECTED-Spirometry was performed according to internationally accepted standards.Trough FEV1 at Week 12 was defined as the mean of the values collected at two time points 30 minutes apart at approximately 24 hours (± 1 hour) after the previous morning dose.Change from baseline in trough FEV1 was calculated as the trough FEV1 value at Week 12 minus the morning trough FEV1 at baseline (mean of the two pre-dose values at 45 and 15 minutes prior to the first dose). All collected values were used in this analyses, regardless if the subject remained on randomized treatment or not, and regardless if the values might potentially be affected by other therapies or not Values not collected remained as missing values and were assumed to be missing at random (MAR) "ALL COLLECTED" and "ON TREATMENT" data are the same. The only difference is in the number of visits included for those participants who may have discontinued randomized treatment but remained in the study." for all endpoints
Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) Week 12
时间窗: Baseline and Week 12
ON TEATMENT-Spirometry was performed according to internationally accepted standards.Trough FEV1 at Week 12 was defined as the mean of the values collected at two time points 30 minutes apart at approximately 24 hours (± 1 hour) after the previous morning dose.Change from baseline in trough FEV1 was calculated as the trough FEV1 value at Week 12 minus the morning trough FEV1 at baseline (mean of the two pre-dose values at 45 and 15 minutes prior to the first dose).Only on-treatment values (which included only data collected while subjects were taking study drug) are used for this analysis. Values affected by other medication use were set to missing. Non-collected or missing data were not imputed for this analysis. Values not collected remained as missing values and were assumed to be missing at random (MAR).
次要结局
- Change From Baseline in Trough Forced Vital Capacity (FVC) Week 12(Baseline and Week 12)
- Standardized Change From Baseline at Week 12 in FEV1 Area Under the Curve (AUC) (0-12) in Substudy Population(Baseline and Week 12)
- Change From Baseline in Health Status Measured by St. George's Respiratory Questionnaire (SGRQ) at Week 12/End of Study(Baseline and Week 12)
- Change in Number of Rescue Medication Puffs Per Day Over the 12-week Double-blind Treatment Period(Week 0-12)
- Change From Baseline in Trough Forced Vital Capacity (FVC) at Week 12(Baseline and Week 12)
- Number of Subjects With Treatment Emergent Adverse Events (TEAE)(Week 0-12)
- Percent of Subjects Who Discontinue Treatment Due to TEAE(Week 0-12)
- Number of Subjects With Major Adverse Cardiac Events (MACE)(Week 0-12)
- Standardized Change From Baseline at Week 12 in FEV1 Area Under the Curve (AUC) (0-12) in the Substudy Population(Baseline and Week 12)
- Change From Baseline in Health Status Measured by St. George's Respiratory Questionnaire (SGRQ) Week 12/End of Study(Baseline and Week 12)
- Percentage of Subjects With Major Cardiac Events (MACE)(Week 0-12)
- Percent of Subjects With Treatment Emergent Serious Adverse Events (SAE)(Week 0-12)
- Number of Subjects Who Discontinue Treatment Due to TEAE(Week 0-12)
- Percent of Subjects With Treatment Emergent Adverse Events (TEAE)(Week 0-12)
- Number of Subjects With Treatment Emergent Serious Adverse Events (SAE)(Week 0-12)
- Incidence Rate Per 100 Person-years of Subjects With Treatment Emergent Adverse Events (TEAE)(Week 0-12)