A 12-week Treatment, Multi-center, Randomized, Double-blind, Parallel-group, Placebo and Active Controlled Study to Assess the Efficacy, Safety, and Tolerability of Indacaterol Maleate / Glycopyrronium Bromide in COPD Patients With Moderate to Severe Airflow Limitation
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 1,001
- 试验地点
- 1
- 主要终点
- Primary: Change From Baseline in Standardized Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC) (0-12 Hours (h))
研究概览
简要总结
This study will assess the efficacy, safety and tolerability of indacaterol maleate/glycopyrronium bromide in patients with moderate to severe airflow limitation.
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 and female patients that have signed informed consent and are >/= 40 years of age.
- •Patients with stable COPD according to GOLD
- •Patients with a post-bronchodilator FEV1 of >/= 30% and < 80% predicted and a post-bronchodilator FEV1/FVC <0.
- •Current or ex-smokers who have a smoking history of at least 10 pack years.
- •Patients with an mMRC grade 2 or greater.
排除标准
- •Patients with Type I or uncontrolled Type II diabetes - Patients with a history of long QT syndrome or whose QTc measured at Visit 101 (Fridericia method) is prolonged (>450 ms for males and females) and confirmed by a central assessor. (These patients should not be re-screened.)
- •Patients who have a clinically significant ECG abnormality at Visit 101 or Visit
- •(These patients should not be re-screened.)
- •Patients with a history of malignancy of any organ system, treated or untreated, within the last five years.
- •Patients with narrow-angle glaucoma, BPH or bladder-neck obstruction or moderate-severe renal impairment or urinary retention.
- •Patients who had a COPD exacerbation within 6 weeks prior to screening.
- •Patients who have a respiratory tract infection within 4 weeks prior to screening.
- •Patients requiring long term oxygen therapy prescribed for more than 12 hr per day.
- •Patients with a history of asthma.
- •Patients with an onset of respiratory symptoms, including COPD diagnosis, prior to age 40 years.
- •Patients with a blood eosinophil count of greater than 600 mm/3 during run-in.
- •Patients with concomitant pulmonary disease.
- •Patients with a diagnosis of alpha-1 anti-trypsin deficiency.
- •Patients with active pulmonary tuberculosis.
- •Patients in the active phase of a pulmonary rehabilitation programme.
- •Other protocol-defined inclusion/exclusion criteria may apply
研究组 & 干预措施
QVA149
27.5/12.5 ug twice daily (b.i.d.) Single Dose Dry Powder Inhaler (SDDPI
干预措施: QVA149 (Drug)
QAB149
27.5 ug b.i.d.
干预措施: QAB149 (Drug)
NVA237
12.5 ug b.i.d.
干预措施: NVA237 (Drug)
Placebo
b.i.d.
干预措施: Placebo (Drug)
结局指标
主要结局
Primary: Change From Baseline in Standardized Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC) (0-12 Hours (h))
时间窗: baseline (BL), 12 weeks
Pulmonary function assessments were performed using centralized spirometry according to international standards. Baseline FEV1 was defined as the average of the pre-dose FEV1 measured at -45 minutes (min) and -15 min at day 1. A mixed model for repeated measures (MMRM), used for this analysis, included terms of treatment, baseline FEV1 measurements, smoking status at baseline, baseline inhaled corticosteroid (ICS) use, region, baseline FEV1 \* visit interaction, and visit, treatment \* visit interaction. Missing values of FEV1 AUC0-12 at Day 1 and Week 12 will not imputed. The trapezoidal rule was used to calculate FEV1 AUC and then normalized to the length of time.
次要结局
- Change From Baseline in St. George's Respiratory Questionnaire (SGRQ) Total Score(BL, 12 Weeks)
- Percentage of Participants With a Clinically Important Improvement of at Least 4 Units in the SGRQ Total Score(12 weeks)
- Change From Baseline in Trough FEV1(BL, day 2, day 86)
- Change From Baseline in Pre-dose Trough FEV1(BL, day 85)
- Change From Baseline in FEV1(BL, Day 1: 5min, 15min, 1h, 2h, 4h, 6h, 8h, 11h55 min; Day 2: 23h15min, 23h45min; Day 15: -45min, -15min, 1h; Day 29: -45 min, -15min, 1h; Day 57: -45min, -15min, 1h; day 85: -45min, -15min, 5min, 15min, 1h, 2h, 4h, 6h, 8h, 11h; day 86: 23h15min; 23h45min)
- Change From Baseline in FVC(BL, Day 1: 5min, 15min, 1h, 2h, 4h, 6h, 8h, 11h55 min; Day 2: 23h15min, 23h45min; Day 15: -45min, -15min, 1h; Day 29: -45 min, -15min, 1h; Day 57: -45min, -15min, 1h; day 85: -45min, -15min, 5min, 15min, 1h, 2h, 4h, 6h, 8h, 11h; day 86: 23h15min; 23h45min)
- Secondary: Change From Baseline in Standardized FEV1 AUC (0-4 h), FEV1 AUC (4-8h), FEV1 AUC (8-12h) and FEV1 AUC (0-12 h)(BL, day 1, 12 weeks)
- Transitional Dyspnea Index (TDI) Focal Score(BL, 12 weeks)
- Secondary: Change From Baseline in Mean Daily Number of Puffs of Rescue Medication(BL, 12 weeks)
- Secondary: Change From Baseline in Mean Total Daily Symptom Score, Mean Daytime Total Symptom Score and Mean Nighttime Total Symptom Score(BL, 12 weeks)