A Randomized, Double-blind, Parallel Group, 26-week Study Evaluating the Efficacy, Safety and Tolerability of NVA237 Given Once or Twice Daily, in Patients With Moderate and Severe Chronic Obstructive Pulmonary Disease
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 776
- 试验地点
- 1
- 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 study is a post-authorization commitment to the European Medicines Agency (EMA). The study serves to determine whether the treatment of patients with stable, symptomatic Chronic Obstructive Pulmonary Disease (COPD) with the investigational drug NVA237 is efficient and safe. The efficacy and safety of the drug was tested for twice daily dosing against once daily dosing.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 41 Years 至 84 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Written informed consent must be obtained before any assessment is performed
- •Male and female adults aged ≥40 years
- •Patients with stable COPD according to the current GOLD strategy (GOLD 2014)
- •Current or ex-smokers who have a smoking history of at least 10 pack years- an ex-smoker may be defined as a subject who has not smoked for ≥ 6 months at screening
- •mMRC grade of at least 2 at Visit 101
- •Patients with airflow limitation indicated by a post-bronchodilator FEV1 ≥ 30 % and < 80 % of the predicted normal, and a post-bronchodilator FEV1/FVC < 0.70 at Visit 101.
排除标准
- •Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test; Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using effective methods of contraception during dosing of study treatment
- •Patients with Type I or uncontrolled Type II diabetes; Patients with a history of long QT syndrome or whose QTc measured at run-in (Fridericia method) is prolonged (>450 ms for males and >460 for females) and confirmed by a central assessor
- •Patients requiring long term oxygen therapy prescribed for >12 h per day; Patients with any history of asthma.
研究组 & 干预措施
NVA237 Twice daily
Patients randomized to this arm received an NVA237 22 μg capsule in the morning and evening for 26 weeks. All participants received salbutamol as rescue medicine.
干预措施: NVA237 (Drug)
NVA237 Once daily
Patients randomized to this arm received an NVA237 44 μg capsule in the morning and a placebo capsule in the evening for 26 weeks. All participants received salbutamol as rescue medicine.
干预措施: Placebo (Drug)
NVA237 Once daily
Patients randomized to this arm received an NVA237 44 μg capsule in the morning and a placebo capsule in the evening for 26 weeks. All participants received salbutamol as rescue medicine.
干预措施: NVA237 (Drug)
NVA237 Once daily
Patients randomized to this arm received an NVA237 44 μg capsule in the morning and a placebo capsule in the evening for 26 weeks. All participants received salbutamol as rescue medicine.
干预措施: Salbutamol (Drug)
NVA237 Twice daily
Patients randomized to this arm received an NVA237 22 μg capsule in the morning and evening for 26 weeks. All participants received salbutamol as rescue medicine.
干预措施: Salbutamol (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, Week 12
Spirometry testing was performed in accordance with American Thoracic Society standards. Trough FEV1 defined as the mean of two measurements at 23 hours 15 minutes and 23 hour 45 minutes post dosing. Baseline FEV1 was defined as the average of the -45 minutes and -15 minutes FEV1 values taken on Day 1. An analysis-of-covariance (ANCOVA) for repeated measurements, also known as mixed model for repeated measures (MMRM), was performed for the change from baseline of trough FEV1 at Week 12. The model included treatment, COPD severity, baseline smoking status, baseline ICS use, region, and visit (Day 1, and Weeks 12 and 26) as factors and baseline FEV1 as a covariate.
次要结局
- Change From Baseline in Area Under The Curve (AUC) for Forced Expiratory Volume in One Second (FEV1) for Different Time Spans Post Dosing at Week 26(Baseline, 0-12 hour, 0-24 hour , 12-24 hour post dose at Week 26)
- Change From Baseline in Total St. George's Respiratory Questionnaire (SGRQ) Score at Week 12 and Week 26(Baseline, 12 Weeks, 26 Weeks)
- Change From Baseline in Area Under The Curve (AUC) for Forced Expiratory Volume in One Second (FEV1) for Different Time Spans Post Dosing at Week 12(Baseline, 0-12 hour, 0-24 hour , 12-24 hour post dose at Week 12)
- Change From Baseline in Area Under The Curve (AUC 0-12 Hour) for Forced Expiratory Volume in One Second (FEV1) Post Dosing at Day 1(Baseline, 0-12 hour post dose at Day 1)
- Percentage of Patients With a Clinically Significant Improvement in St George Respiratory Questionnaire at Week 12 and Week 26(Baseline, 12 Weeks, 26 Weeks)
- Change From Baseline in Transitional Dyspnea Index (TDI) Focal Score at Week 12 and Week 26(Baseline, 12 Weeks, 26 Weeks)
- Percentage of Patients With a Clinically Important Improvement on Transitional Dyspnea Index (TDI) Focal Score at Week 12 and Week 26(Baseline, 12 Weeks, 26 Weeks)
- Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) at Day 1 and Week 26(Baseline, Day 1, Week 26)
- Change From Baseline in Forced Vital Capacity (FVC) at Individual Timepoints at Week 26(Baseline, Week 26 (Day 183-184))
- Change From Baseline in Inspiratory Capacity (IC) at Individual Timepoints at Week 26(Baseline, Week 26 (Day 183-184))
- Change From Baseline in Forced Expiratory Volume in One Second (FEV1) at Individual Timepoints at Week 26(Baseline, Week 26 (Day 183-184))
- Change From Baseline in the Percentage of Days With no Rescue Medication Use Over the 26 Weeks(Baseline, 26 Weeks)
- Change From Baseline in Mean Daily COPD Symptom Score at Week 26(Baseline, 26 Weeks)
- Number of Patients With Adverse Events, Serious Adverse Events and Death(26 Weeks)