A 52-week Treatment, Randomized, Double-blind, Placebo-controlled, With Open-label Tiotropium, Parallel-group Study to Assess the Efficacy, Safety, and Tolerability of Glycopyrronium Bromide (NVA237) in Patients With Chronic Obstructive Pulmonary Disease
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Novartis
- 入组人数
- 1,066
- 试验地点
- 4
- 主要终点
- Trough Forced Expiratory Volume in 1 Second (FEV1) at Week 12
研究概览
简要总结
This study was designed to investigate the 1 year efficacy and safety of the 50 µg once daily (od) dose of glycopyrronium bromide (NVA237) in patients with moderate to severe chronic obstructive pulmonary disease.
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
- Triple (Participant, Care Provider, Investigator)
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 adults aged ≥ 40 years, who have signed an Informed Consent Form prior to initiation of any study-related procedure.
- •Patients with moderate to severe stable chronic obstructive pulmonary disease (COPD, Stage II or Stage III) according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) Guidelines
- •Current or ex-smokers who have a smoking history of at least 10 pack years.
- •Patients with a post-bronchodilator forced expiratory volume in 1 second (FEV1) ≥ 30% and < 80% of the predicted normal, and post-bronchodilator FEV1/forced vital capacity (FVC) < 0.7 at Visit 2 (Day -14).
- •Patients, according to daily electronic diary data between Visit 2 (Day -14) and Visit 3 (Day 1), with a total score of 1 or more on at least 4 of the last 7 days prior to Visit 3 (Day 1).
排除标准
- •Pregnant women or nursing mothers (pregnancy confirmed by positive urine pregnancy test).
- •Women of child-bearing potential, unless using an approved method of medical or surgical contraception.
- •Patients requiring long term oxygen therapy (> 15 h a day) on a daily basis for chronic hypoxemia, or who have been hospitalized for an exacerbation of their airways disease in the 6 weeks prior to Visit 1 (Day -21) or between Visit 1 (Day -21) and Visit 3 (Day 1).
- •Patients who have had a respiratory tract infection within 6 weeks prior to Visit 1 (Day -21).
- •Patients who, in the judgment of the investigator or the responsible Novartis personnel, have a clinically relevant laboratory abnormality or a clinically significant condition.
- •Patients with any history of asthma indicated by (but not limited to) a blood eosinophil count > 600/mm^3 (at Visit 1, Day -21) and onset of symptoms prior to age 40 years.
- •Patients with a history of long QT syndrome or whose QTc measured at Visit 1 (Day -21) (Fridericia method) is prolonged (> 450 ms for males or > 470 ms for females.
- •Other protocol-defined inclusion/exclusion criteria may apply to the study.
研究组 & 干预措施
Glycopyrronium bromide 50 μg
Patients inhaled glycopyrronium bromide 50 μg once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
干预措施: Glycopyrronium bromide (Drug)
Placebo to glycopyrronium bromide
Patients inhaled placebo to glycopyrronium bromide once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
干预措施: Placebo to glycopyrronium bromide (Drug)
Tiotropium 18 μg
Patients inhaled tiotropium 18 μg once daily in the morning between 8:00 AM and 10:00 AM via a single-dose dry-powder inhaler (SDDPI) for 52 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
干预措施: Tiotropium (Drug)
结局指标
主要结局
Trough Forced Expiratory Volume in 1 Second (FEV1) at Week 12
时间窗: Week 12
FEV1 was measured with spirometry conducted according to internationally accepted standards. Trough FEV1 was defined as the average of measurements made 23 hours 15 minutes and 23 hours 45 minutes post-dose. The analysis included baseline FEV1 measurement, baseline inhaled corticosteroid use (Yes/No), FEV1 prior to inhalation of short-acting β2 agonist (SABA), and FEV1 45 min post-inhalation of SABA as covariates.
次要结局
- Transition Dyspnea Index (TDI) at Week 26(Week 26)
- Health-related Quality of Life (QoL) Assessed With the St. George Respiratory Questionnaire (SGRQ) at Week 52(Week 52)
- Time to First Moderate or Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbation During the Study (Baseline to Week 52)(Baseline to Week 52 (patients with no moderate or severe exacerbations who completed the study were censored at the final visit date, which may have exceeded 52 weeks))
- Change From Baseline in the Mean Daily Number of Puffs of Rescue Medication Taken During the Study (Baseline to Week 52)(Baseline to Week 52)
- Trough Forced Expiratory Volume in 1 Second (FEV1) at Day 1, Week 26, and Week 52(Day 1, Week 26, and Week 52)
- Trough Forced Vital Capacity (FVC) at Day 1, Week 12, Week 26, and Week 52(Day 1, Week 12, Week 26, and Week 52)
- Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52(5, 15, and 30 minutes; 1, 2, 3, 4, 6, 8, 10, and 12 hours; 23 hours 15 minutes; and 23 hours 45 minutes post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52)
- Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52(5, 15, and 30 minutes; 1, 2, 3, 4, 6, 8, 10, and 12 hours; 23 hours 15 minutes; and 23 hours 45 minutes post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52)
- Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post Dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52(5, 15, and 30 minutes; and 1, 2, 3, 4 hours post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52)
- Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52(5, 15, and 30 minutes; and 1, 2, 3, 4 hours post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52)
- Forced Expiratory Volume in 1 Second (FEV1) Standardized (With Respect to Length of Time) Area Under the Curve (AUC) From 5 Minutes to 4 Hours Post-dose at Day 1 and Weeks 12, 26, and 52(From 5 minutes to 4 hours post-dose at Day 1 and Weeks 12, 26, and 52)
- Forced Expiratory Volume in 1 Second (FEV1) Standardized (With Respect to Length of Time) Area Under the Curve (AUC) From 5 Minutes to 12 Hours Post-dose at Day 1 and Weeks 12 and 52(From 5 minutes to 12 hours post-dose at Day 1 and Weeks 12 and 52)
- Forced Expiratory Volume in 1 Second (FEV1) Standardized (With Respect to Length of Time) Area Under the Curve (AUC) From 5 Minutes to 23 Hours 45 Minutes and From 12 Hours to 23 Hours 45 Minutes Post-dose at Weeks 12 and 52(From 5 minutes to 23 hours 45 minutes post-dose at Weeks 12 and 52)
- Number of Moderate or Severe Exacerbations of Chronic Obstructive Pulmonary Disease (COPD) Per Year During the Study (Baseline to Week 52)(Baseline to Week 52)
- Percentage of Patients Who Experienced a Moderate or Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbation During the Study (Baseline to Week 52)(Baseline to Week 52)
- Percentage of Nights With "no Nighttime Awakenings" During the Study (Baseline to Week 52)(Baseline to Week 52)
- Percentage of Days With "no Daytime Symptoms" During the Study (Baseline to Week 52)(Baseline to Week 52)
- Percentage of "Days Able to Perform Usual Daily Activities" During the Study (Baseline to Week 52)(Baseline to Week 52)
- Change From Baseline in the Mean Daily Total Symptom Score During the Study (Baseline to Week 52)(Baseline to Week 52)