A Phase IIb, Randomized, Double-blind, Placebo-controlled Study to Assess the Efficacy, Safety, and Pharmacokinetics of Glycopyrrolate Inhalation Solution Over 1 Week in Subjects With COPD
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 46
- 试验地点
- 7
- 主要终点
- Change From Average Baseline in Morning Trough Forced Expiratory Volume in 1 Second (FEV1)
研究概览
简要总结
This study is a randomized, double-blind, placebo-controlled complete block cross-over study designed to assess the efficacy, safety, and pharmacokinetics of 3 dose levels of glycopyrrolate inhalation solution delivered twice daily via standard jet nebulizer over three 1-week active treatment periods and one 1-week placebo period in subjects with chronic obstructive pulmonary disease (COPD).
详细描述
Participants enrolled will be expected to participate for approximately 10 weeks;1-2 weeks for screening, four 1-week treatment periods separated by 1 week of washout between each treatment, and 1 week of follow-up. Participants will be randomized to a treatment sequence, 1-4, which will determine the order that they receive the dose levels during the four treatment periods of the study. Neither participants nor study staff will know which dose a participant is receiving in any given treatment period. All participants will receive all 4 dose levels and it is expected that each participant completes all four treatment periods in their assigned sequence. The primary objective of this study is to evaluate the bronchodilator effect of twice daily inhaled glycopyrrolate solution over a dose range administered by standard jet nebulizer in subjects with COPD on Day 7, to support the selection of the glycopyrrolate doses for further clinical development in a fixed-dose combination with ensifentrine.
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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 40 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Males are eligible to participate if they agree to use contraception from Screening and throughout the study and for at least 30 days after the last dose of blinded study medication.
- •Females are eligible to participate if they are not pregnant, not breastfeeding, and ≥ 1 of the following conditions apply:
- •Not a woman of childbearing potential (WOCBP) OR
- •A WOCBP who agrees to follow the contraceptive guidance from Screening and throughout the study and for at least 30 days after the last dose of blinded study medication.
- •Current or former cigarette smokers with a history of cigarette smoking ≥ 10 pack years at Screening [number of pack years = (number of cigarettes per day / 20) × number of years smoked (e.g., 20 cigarettes per day for 10 years, or 10 cigarettes per day for 20 years)]. Pipe and/or cigar use cannot be used to calculate pack-year history. Former smokers are defined as those who have stopped smoking for at least 6 months prior to Screening. Smoking cessation programs are permitted during the study.
- •Subjects with an established clinical history of COPD as defined by the American Thoracic Society (ATS)/European Respiratory Society (ERS) guidelines with symptoms compatible with COPD.
- •Post-bronchodilator (4 puffs of salbutamol) spirometry at Screening demonstrating both the following:
- •FEV1/forced vital capacity (FVC) ratio of < 0.70 AND
- •FEV1 ≥ 30 % and ≤ 70% of predicted normal
- •A posterior-anterior chest x-ray (CXR) at Screening or within 12 months prior to Screening showing no clinically significant abnormalities unrelated to COPD. If a CXR within the past 12 months is not available but a computed tomography (CT) scan within the same time period is available, the CT scan may be reviewed in place of a CXR.
- •Capable of withdrawing from short-acting bronchodilators for 4 hours prior to spirometry testing and from BID LABA ± ICS therapy for 24 hours prior to spirometry.
- •Capable of using the study nebulizer correctly.
- •Ability to perform acceptable spirometry in accordance with ATS/ERS guidelines
- •Willing and able to attend all study visits and adhere to all study assessments and procedures.
排除标准
- •Concomitant clinically significant pulmonary disease other than COPD (i.e., asthma, tuberculosis, lung cancer, bronchiectasis, sarcoidosis, lung fibrosis, interstitial lung diseases, sleep apnea (unless controlled with stable continuous positive airway pressure [CPAP] use), known alpha-1 antitrypsin deficiency, core pulmonale or other non-specific pulmonary disease).
- •Within 6 months prior to Screening:
- •COPD exacerbation requiring hospitalization.
- •Use of therapies for COPD exacerbation (e.g., oral, intravenous, or intramuscular glucocorticoids).
- •Lower respiratory tract infection within 6 weeks of Screening or an active infection at Screening.
- •History of life-threatening COPD, including Intensive Care Unit admission and/or requiring intubation.
- •Previous lung resection or lung reduction surgery within 1-year of Screening.
- •Long term oxygen use defined as oxygen therapy prescribed for greater than 12 hours per day. As needed oxygen use (≤ 12 hours per day) is not exclusionary.
- •Severe comorbidities including unstable cardiac, or any other clinically significant medical conditions including uncontrolled diseases 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.
- •History of or clinically significant on-going 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, salbutamol or glycopyrrolate or any of its excipients/components, anticholinergic agents, or sympathomimetic amines.
- •Pulmonary rehabilitation unless such treatment has been stable from 4 weeks prior to Screening (Visit 1) and remains stable during the study. Pulmonary rehabilitation programs should not be started or completed during participation in the study.
- •Major surgery (requiring general anesthesia) in the 6 weeks prior to Screening, lack of full recovery from surgery at Screening, or planned surgery through the end of the study.
- •History of or current malignancy of any organ system, treated or untreated within the past 5 years, except for localized basal or squamous cell carcinoma of the skin.
- •Current or history of drug or alcohol abuse within the past 5 years.
- •Estimated glomerular filtration rate (eGFR) < 30 mL/min.
- •Women who are breast feeding.
- •Use of an experimental drug within 30 days or within 5 half-lives of Screening, whichever is longer, and/or participation in a study treatment-free follow-up phase of a clinical study within 30 days prior to Screening.
- •Use of an experimental medical device or participation in a follow-up phase of an experimental medical device clinical study within 30 days prior to Screening.
- •Affiliation with the investigator site, including an Investigator, Sub-Investigator, study coordinator, study nurse, other employee of participating investigator or study site or a family member of the aforementioned.
研究组 & 干预措施
Dose Level C
The treatment period will be 7 days, followed by a 7-day washout period, before beginning the next treatment in the sequence they were assigned to
干预措施: Glycopyrrolate (14 μg) (Drug)
Dose Level A
The treatment period will be 7 days, followed by a 7-day washout period, before beginning the next treatment in the sequence they were assigned to
干预措施: Glycopyrrolate (85 μg) (Drug)
Dose Level B
The treatment period will be 7 days, followed by a 7-day washout period, before beginning the next treatment in the sequence they were assigned to
干预措施: Glycopyrrolate (42.5 μg) (Drug)
Dose Level D
The treatment period will be 7 days, followed by a 7-day washout period, before beginning the next treatment in the sequence they were assigned to
干预措施: Placebo (Drug)
结局指标
主要结局
Change From Average Baseline in Morning Trough Forced Expiratory Volume in 1 Second (FEV1)
时间窗: Baseline (pre-dose for each treatment period) and Day 7
次要结局
- Change From Average Baseline FEV1 to Average Peak FEV1 Measured Over 4 Hours(Baseline (pre-dose for each treatment period) and Day 7)
- Change From Average Baseline FEV1 to Average FEV1 Area Under the Curve Versus Time From Time 0 to 4 Hours (AUC0-4h)(Baseline (pre-dose for each treatment period) and Day 7)
- Change From Average Baseline FEV1 to Average FEV1 Area Under the Curve Versus Time From Time 0 to 12 Hours (AUC0-12h)(Baseline (pre-dose for each treatment period) and Day 7)
- Change From Average Baseline FEV1 to Evening Trough FEV1(Baseline (pre-dose for each treatment period) and Day 7)
- Change From Average Baseline FEV1 to Peak FEV1 Measured Over 4 Hours After First Dose(Baseline (pre-dose) and Day 1)
- Change From Average Baseline FEV1 to Average FEV1 AUC0-4h Measured After First Dose(Baseline (pre-dose) and Day 1)
- Number of Treatment Emergent Adverse Events (TEAEs)(From first dose through the follow-up contact (approximately 8 weeks per participant). Overall safety data was collected for 5 months total.)
- Glycopyrronium Free Base AUC0-12h(After morning dose Day 7)
- Glycopyrronium Free Base Maximum Plasma Drug Concentration (Cmax)(After morning dose Day 7)
- Glycopyrronium Free Base Time to Maximum Plasma Drug Concentration (Tmax)(After morning dose Day 7)