Chronic Obstructive Pulmonary Disease (COPD)
Conditions
Keywords
COPD, Chronic Obstructive Pulmonary Disease, Indacaterol, QVA149
Brief summary
An investigational inhalation product (QVA149) for the treatment of patients with Chronic Obstructive Pulmonary Disease (COPD) is being developed. This 14 day study will investigate the effect on heart rate and cardiovascular effects to ensure the product is safe.
Interventions
Inhalation capsule delivered via a single dose dry powder inhaler in the morning for 14 days.
DRUGindacaterol
Inhalation capsule delivered via a single dose dry powder inhaler in the morning for 14 days.
DRUGglycopyrrolate
Inhalation capsule delivered via a single dose dry powder inhaler in the morning for 14 days.
DRUGplacebo
Inhalation capsule delivered via a single dose dry powder inhaler in the morning for 14 days.
Sponsors
Novartis
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Consented male or female adults aged ≥40 years * Moderate to severe stable Chronic Obstructive Pulmonary Disease (COPD) according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) Guidelines (2006) * Patients who have smoking history of at least 10 pack years * Patients with a post-bronchodilator Forced Expiratory Volume in one second (FEV1) ≥30% and \<80% of the predicted normal and post-bronchodilator FEV1/Forced vital capacity (FVC) \<0.70 at Visit 1 and Visit 3
Exclusion criteria
* Pregnant or nursing (lactating) women * Patients requiring long term oxygen therapy (\> 15 hours a day) on a daily basis for chronic hypoxemia, or who have been hospitalized or visited an emergency room for a COPD exacerbation in the 6 weeks prior to screening (Visit 1) or during the screening period * Patients who had a respiratory tract infection within 6 weeks of Visit 1 or at screening * Concomitant pulmonary disease, pulmonary tuberculosis (TB) (unless chest x-ray confirms no longer active) or clinically significant bronchiectasis * Any history of asthma * Patients who have clinically relevant lab abnormalities / conditions such as (but not limited to) long term prednisone therapy, unstable ischemic heart disease, left ventricular failure, history of myocardial infarction, arrhythmia (excluding stable atrial fibrillation \[AF\]), uncontrolled hypertension, narrow-angle glaucoma, symptomatic prostatic hyperplasia or bladder-neck obstruction or moderate to severe renal impairment, uncontrolled hypo- and hyperthyroidism, hypokalemia, hyperadrenergic state or any condition which might compromise patient safety or compliance, interfere with evaluation, or preclude completion of the study * Patients with a history of cardiac failure, life threatening arrhythmias (screening Holter) and acute ischemic changes (screening ECG) * Patients with a history of long QT syndrome or whose QTc (Fridericia method) interval measured at screening (Visit 1) is prolonged (\>450 ms for males or \>470 for females) * History of malignancy of any organ system, treated or untreated within the past 5 years * Uncontrolled Type I / Type II Diabetes or blood glucose outside the normal range or Hemoglobin A1C (HbA1c) \>8.0% of total hemoglobin measured at Visit 1 Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Mean 24 Hour Heart Rate at Day 14 | Baseline, Day 14 | Heart rate was assessed by Holter monitoring and was measured over a 24 hour period at day 14. Heart rate was defined as the average value over the 24 hour monitoring period. The baseline measurement was the average heart rate taken from the 24 hour Holter monitoring period performed at screening or the last 24-hour period before taking the first dose of study drug. Least square means are based on the analysis of covariance: 24 hours mean heart rate = center + treatment + baseline value + Forced Expiratory Volume in one second (FEV1) before inhalation of salbutamol/albuterol + FEV1 30 min post salbutamol/albuterol + error. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Mean 24 Hour Heart Rate at Day 1 | Baseline, Day 1 | Heart rate was assessed by Holter monitoring and was measured over a 24 hour period at day 1. Heart rate was defined as the average value over the 24 hour monitoring period. The baseline measurement was the average heart rate taken from the 24 hour Holter monitoring period performed at screening or the last 24-hour period before taking the first dose of study drug. Least squares means are based on the analysis of covariance: 24 hours mean heart rate = center + treatment + baseline value + Forced Expiratory Volume in one second (FEV1) before inhalation of salbutamol/albuterol + FEV1 30 min after inhalation of salbutamol/albuterol + error. |
| Trough Forced Vital Capacity (FVC) at Day 1 and Day 14 | Day 1 and Day 14 | Spirometry testing was performed in accordance with American Thoracic Society standards. Trough FVC was defined as the mean of two measurements at 23 hours 15 minutes and the 23 hours 45 minutes post dosing. Baseline was defined as the mean of the two values taken at 45 minutes and 15 minutes prior to dosing at day 1. Analysis of covariance: FVC parameter = center + treatment + baseline FVC + FEV1 before inhalation of salbutamol/albuterol + FEV1 30 min after inhalation of salbutamol/albuterol + error. |
| Trough Forced Expiratory Volume in 1 Second (FEV1) at Day 1 and Day 14 | Day 1, Day 14 | Spirometry testing was performed in accordance with American Thoracic Society standards. Trough FEV1 was defined as the mean of two measurements at 23 hours 15 minutes and 23 hour 45 minutes post dosing. Baseline is defined as the mean of the two values taken at 45 minutes and 15 minutes prior to dosing at day 1. Least square means are based on the analysis of covariance: response variable=center + treatment + baseline value + Forced Expiratory Volume in one second (FEV1) before inhalation of salbutamol/albuterol + FEV1 30 minutes post inhalation of salbutamol/albuterol. |
| Change From Baseline in QTc (Fridericia's Formula) at Day 7 | Baseline, Day 7 | The change from baseline in QTc at 30 minutes and 2 hours post dose on day 7. QT calculated (QTc) was calculated from the QT interval and RR (in seconds) using Fridericia's formula: QTc = QT / 3√ RR. Least square means are based on the analysis of covariance: response variable = center + treatment + baseline value + FEV1 before inhalation of salbutamol/albuterol + FEV1 30 min post inhalation of salbutamol/albuterol. |
| Change From Baseline in QTc (Fridericia's Formula) at Day 14 | Baseline, Day 14 | The change from baseline in QTc at 30 minutes, 4 hours and 23 hours 45 minutes post dose on day 14. QT calculated (QTc) was calculated from the QT interval and RR (in seconds) using Fridericia's formula: QTc = QT / 3√ RR. Least square means are based on the analysis of covariance: response variable = center + treatment + baseline value + FEV1 before inhalation of salbutamol/albuterol + FEV1 30 minutes post inhalation of salbutamol/albuterol. |
| Change From Baseline in QTc (Fridericia's Formula) at Day 1 | Baseline, Day 1 | The change from baseline in QTc at 30 minutes, 4 hours and 23 hours 45 minutes post dose on day 1. QT calculated (QTc) was calculated from the QT interval and RR (in seconds) using Fridericia's formula: QTc = QT / 3√ RR. Least square means are based on the analysis of covariance: response variable = center + treatment + baseline value + FEV1 before inhalation of salbutamol/albuterol + FEV1 30 min post inhalation of salbutamol/albuterol. |
Countries
Australia, Belgium, Canada, France, Germany, Italy, Spain, Turkey (Türkiye)
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Indacaterol/Glycopyrrolate 600/100 μg Two capsules indacaterol/glycopyrrolate 300/50 μg delivered via a single dose dry powder inhaler in the morning for 14 days.
The use of salbutamol/albuterol as rescue medication was permitted throughout the study. | 49 |
| Indacaterol/Glycopyrrolate 300/100 μg One capsule indacaterol/glycopyrrolate 300/100 μg and one placebo capsule delivered via a single dose dry powder inhaler in the morning for 14 days.
The use of salbutamol/albuterol as rescue medication was permitted throughout the study. | 51 |
| Indacaterol/Glycopyrrolate 150/100 μg One capsule indacaterol/glycopyrrolate 150/50 μg and one capsule 50 μg glycopyrrolate delivered via a single dose dry powder inhaler in the morning for 14 days.
The use of salbutamol/albuterol as rescue medication was permitted throughout the study. | 51 |
| Indacaterol 300 μg One capsule indacaterol 300 μg and one placebo capsule delivered via s single dose dry powder inhaler in the morning for 14 days.
The use of salbutamol/albuterol as rescue medication was permitted throughout the study. | 51 |
| Placebo Two placebo capsules delivered via a single dose dry powder inhaler in the morning for 14 days.
The use of salbutamol/albuterol as rescue medication was permitted throughout the study. | 53 |
| Total | 255 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Abnormal test procedure result(s) | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Administrative problems | 0 | 0 | 0 | 1 | 1 |
| Overall Study | Adverse Event | 1 | 1 | 4 | 1 | 2 |
| Overall Study | Lost to Follow-up | 1 | 1 | 0 | 0 | 0 |
| Overall Study | Protocol deviation | 1 | 1 | 0 | 1 | 0 |
| Overall Study | Subject withdrew consent | 2 | 0 | 1 | 1 | 1 |
Baseline characteristics
| Characteristic | Indacaterol/Glycopyrrolate 600/100 μg | Indacaterol/Glycopyrrolate 300/100 μg | Indacaterol/Glycopyrrolate 150/100 μg | Indacaterol 300 μg | Placebo | Total |
|---|---|---|---|---|---|---|
| Age Continuous | 65.7 years STANDARD_DEVIATION 9.34 | 63.7 years STANDARD_DEVIATION 8.94 | 60.9 years STANDARD_DEVIATION 8.58 | 64.5 years STANDARD_DEVIATION 9.75 | 64.3 years STANDARD_DEVIATION 8.95 | 63.8 years STANDARD_DEVIATION 9.19 |
| Sex: Female, Male Female | 11 Participants | 10 Participants | 15 Participants | 10 Participants | 14 Participants | 60 Participants |
| Sex: Female, Male Male | 38 Participants | 41 Participants | 36 Participants | 41 Participants | 39 Participants | 195 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 5 / 49 | 6 / 51 | 10 / 51 | 7 / 51 | 4 / 53 |
| serious Total, serious adverse events | 2 / 49 | 0 / 51 | 2 / 51 | 0 / 51 | 1 / 53 |
Outcome results
Primary
Change From Baseline in Mean 24 Hour Heart Rate at Day 14
Heart rate was assessed by Holter monitoring and was measured over a 24 hour period at day 14. Heart rate was defined as the average value over the 24 hour monitoring period. The baseline measurement was the average heart rate taken from the 24 hour Holter monitoring period performed at screening or the last 24-hour period before taking the first dose of study drug. Least square means are based on the analysis of covariance: 24 hours mean heart rate = center + treatment + baseline value + Forced Expiratory Volume in one second (FEV1) before inhalation of salbutamol/albuterol + FEV1 30 min post salbutamol/albuterol + error.
Time frame: Baseline, Day 14
Population: Safety Population includes all patients who received at least one dose of study drug. Participants with less than 18 hours quality recording time data were excluded from this analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Indacaterol/Glycopyrrolate 600/100 μg | Change From Baseline in Mean 24 Hour Heart Rate at Day 14 | -0.113 beats per minute | Standard Error 0.9967 |
| Indacaterol/Glycopyrrolate 300/100 μg | Change From Baseline in Mean 24 Hour Heart Rate at Day 14 | 0.787 beats per minute | Standard Error 0.8975 |
| Indacaterol/Glycopyrrolate 150/100 μg | Change From Baseline in Mean 24 Hour Heart Rate at Day 14 | -0.230 beats per minute | Standard Error 0.9567 |
| Indacaterol 300 μg | Change From Baseline in Mean 24 Hour Heart Rate at Day 14 | 0.240 beats per minute | Standard Error 0.9373 |
| Placebo | Change From Baseline in Mean 24 Hour Heart Rate at Day 14 | 0.170 beats per minute | Standard Error 0.876 |
Secondary
Change From Baseline in Mean 24 Hour Heart Rate at Day 1
Heart rate was assessed by Holter monitoring and was measured over a 24 hour period at day 1. Heart rate was defined as the average value over the 24 hour monitoring period. The baseline measurement was the average heart rate taken from the 24 hour Holter monitoring period performed at screening or the last 24-hour period before taking the first dose of study drug. Least squares means are based on the analysis of covariance: 24 hours mean heart rate = center + treatment + baseline value + Forced Expiratory Volume in one second (FEV1) before inhalation of salbutamol/albuterol + FEV1 30 min after inhalation of salbutamol/albuterol + error.
Time frame: Baseline, Day 1
Population: Safety Population includes all patients who received at least one dose of study drug. Participants with less than 18 hours quality recording time data were excluded from this analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Indacaterol/Glycopyrrolate 600/100 μg | Change From Baseline in Mean 24 Hour Heart Rate at Day 1 | -2.877 beats per minute | Standard Error 0.879 |
| Indacaterol/Glycopyrrolate 300/100 μg | Change From Baseline in Mean 24 Hour Heart Rate at Day 1 | -2.770 beats per minute | Standard Error 0.8244 |
| Indacaterol/Glycopyrrolate 150/100 μg | Change From Baseline in Mean 24 Hour Heart Rate at Day 1 | -0.547 beats per minute | Standard Error 0.8208 |
| Indacaterol 300 μg | Change From Baseline in Mean 24 Hour Heart Rate at Day 1 | -1.849 beats per minute | Standard Error 0.8211 |
| Placebo | Change From Baseline in Mean 24 Hour Heart Rate at Day 1 | -0.329 beats per minute | Standard Error 0.8181 |
Secondary
Change From Baseline in QTc (Fridericia's Formula) at Day 1
The change from baseline in QTc at 30 minutes, 4 hours and 23 hours 45 minutes post dose on day 1. QT calculated (QTc) was calculated from the QT interval and RR (in seconds) using Fridericia's formula: QTc = QT / 3√ RR. Least square means are based on the analysis of covariance: response variable = center + treatment + baseline value + FEV1 before inhalation of salbutamol/albuterol + FEV1 30 min post inhalation of salbutamol/albuterol.
Time frame: Baseline, Day 1
Population: Safety Population includes all patients who received at least one dose of study drug.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Indacaterol/Glycopyrrolate 600/100 μg | Change From Baseline in QTc (Fridericia's Formula) at Day 1 | 30 minutes | 1.6 milliseconds | Standard Error 1.58 |
| Indacaterol/Glycopyrrolate 600/100 μg | Change From Baseline in QTc (Fridericia's Formula) at Day 1 | 23 hours 45 minutes | 2.7 milliseconds | Standard Error 1.77 |
| Indacaterol/Glycopyrrolate 600/100 μg | Change From Baseline in QTc (Fridericia's Formula) at Day 1 | 4 hours | 2.8 milliseconds | Standard Error 1.67 |
| Indacaterol/Glycopyrrolate 300/100 μg | Change From Baseline in QTc (Fridericia's Formula) at Day 1 | 4 hours | 0.5 milliseconds | Standard Error 1.56 |
| Indacaterol/Glycopyrrolate 300/100 μg | Change From Baseline in QTc (Fridericia's Formula) at Day 1 | 30 minutes | 1.2 milliseconds | Standard Error 1.48 |
| Indacaterol/Glycopyrrolate 300/100 μg | Change From Baseline in QTc (Fridericia's Formula) at Day 1 | 23 hours 45 minutes | -1.7 milliseconds | Standard Error 1.66 |
| Indacaterol/Glycopyrrolate 150/100 μg | Change From Baseline in QTc (Fridericia's Formula) at Day 1 | 4 hours | 2.4 milliseconds | Standard Error 1.58 |
| Indacaterol/Glycopyrrolate 150/100 μg | Change From Baseline in QTc (Fridericia's Formula) at Day 1 | 30 minutes | 1.4 milliseconds | Standard Error 1.5 |
| Indacaterol/Glycopyrrolate 150/100 μg | Change From Baseline in QTc (Fridericia's Formula) at Day 1 | 23 hours 45 minutes | -0.1 milliseconds | Standard Error 1.67 |
| Indacaterol 300 μg | Change From Baseline in QTc (Fridericia's Formula) at Day 1 | 30 minutes | 3.1 milliseconds | Standard Error 1.47 |
| Indacaterol 300 μg | Change From Baseline in QTc (Fridericia's Formula) at Day 1 | 23 hours 45 minutes | -2.1 milliseconds | Standard Error 1.71 |
| Indacaterol 300 μg | Change From Baseline in QTc (Fridericia's Formula) at Day 1 | 4 hours | 1.1 milliseconds | Standard Error 1.6 |
| Placebo | Change From Baseline in QTc (Fridericia's Formula) at Day 1 | 4 hours | -2.3 milliseconds | Standard Error 1.52 |
| Placebo | Change From Baseline in QTc (Fridericia's Formula) at Day 1 | 30 minutes | -1.6 milliseconds | Standard Error 1.44 |
| Placebo | Change From Baseline in QTc (Fridericia's Formula) at Day 1 | 23 hours 45 minutes | -2.3 milliseconds | Standard Error 1.62 |
Secondary
Change From Baseline in QTc (Fridericia's Formula) at Day 14
The change from baseline in QTc at 30 minutes, 4 hours and 23 hours 45 minutes post dose on day 14. QT calculated (QTc) was calculated from the QT interval and RR (in seconds) using Fridericia's formula: QTc = QT / 3√ RR. Least square means are based on the analysis of covariance: response variable = center + treatment + baseline value + FEV1 before inhalation of salbutamol/albuterol + FEV1 30 minutes post inhalation of salbutamol/albuterol.
Time frame: Baseline, Day 14
Population: Safety Population includes all patients who received at least one dose of study drug.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Indacaterol/Glycopyrrolate 600/100 μg | Change From Baseline in QTc (Fridericia's Formula) at Day 14 | 30 minutes | 2.4 milliseconds | Standard Error 1.79 |
| Indacaterol/Glycopyrrolate 600/100 μg | Change From Baseline in QTc (Fridericia's Formula) at Day 14 | 23 hours 45 minutes | 0.5 milliseconds | Standard Error 1.94 |
| Indacaterol/Glycopyrrolate 600/100 μg | Change From Baseline in QTc (Fridericia's Formula) at Day 14 | 4 hours | 2.8 milliseconds | Standard Error 1.9 |
| Indacaterol/Glycopyrrolate 300/100 μg | Change From Baseline in QTc (Fridericia's Formula) at Day 14 | 4 hours | -0.1 milliseconds | Standard Error 1.76 |
| Indacaterol/Glycopyrrolate 300/100 μg | Change From Baseline in QTc (Fridericia's Formula) at Day 14 | 30 minutes | -0.6 milliseconds | Standard Error 1.64 |
| Indacaterol/Glycopyrrolate 300/100 μg | Change From Baseline in QTc (Fridericia's Formula) at Day 14 | 23 hours 45 minutes | -2.9 milliseconds | Standard Error 1.81 |
| Indacaterol/Glycopyrrolate 150/100 μg | Change From Baseline in QTc (Fridericia's Formula) at Day 14 | 4 hours | 3.1 milliseconds | Standard Error 1.85 |
| Indacaterol/Glycopyrrolate 150/100 μg | Change From Baseline in QTc (Fridericia's Formula) at Day 14 | 30 minutes | 1.6 milliseconds | Standard Error 1.7 |
| Indacaterol/Glycopyrrolate 150/100 μg | Change From Baseline in QTc (Fridericia's Formula) at Day 14 | 23 hours 45 minutes | 0.4 milliseconds | Standard Error 1.95 |
| Indacaterol 300 μg | Change From Baseline in QTc (Fridericia's Formula) at Day 14 | 30 minutes | -1.2 milliseconds | Standard Error 1.69 |
| Indacaterol 300 μg | Change From Baseline in QTc (Fridericia's Formula) at Day 14 | 23 hours 45 minutes | -3.6 milliseconds | Standard Error 1.88 |
| Indacaterol 300 μg | Change From Baseline in QTc (Fridericia's Formula) at Day 14 | 4 hours | -2.6 milliseconds | Standard Error 1.81 |
| Placebo | Change From Baseline in QTc (Fridericia's Formula) at Day 14 | 4 hours | -0.1 milliseconds | Standard Error 1.73 |
| Placebo | Change From Baseline in QTc (Fridericia's Formula) at Day 14 | 30 minutes | 0.2 milliseconds | Standard Error 1.62 |
| Placebo | Change From Baseline in QTc (Fridericia's Formula) at Day 14 | 23 hours 45 minutes | -1.6 milliseconds | Standard Error 1.77 |
Secondary
Change From Baseline in QTc (Fridericia's Formula) at Day 7
The change from baseline in QTc at 30 minutes and 2 hours post dose on day 7. QT calculated (QTc) was calculated from the QT interval and RR (in seconds) using Fridericia's formula: QTc = QT / 3√ RR. Least square means are based on the analysis of covariance: response variable = center + treatment + baseline value + FEV1 before inhalation of salbutamol/albuterol + FEV1 30 min post inhalation of salbutamol/albuterol.
Time frame: Baseline, Day 7
Population: Safety Population includes all patients who received at least one dose of study drug.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Indacaterol/Glycopyrrolate 600/100 μg | Change From Baseline in QTc (Fridericia's Formula) at Day 7 | 30 minutes | 4.1 milliseconds | Standard Error 1.91 |
| Indacaterol/Glycopyrrolate 600/100 μg | Change From Baseline in QTc (Fridericia's Formula) at Day 7 | 2 hours | 2.6 milliseconds | Standard Error 2.17 |
| Indacaterol/Glycopyrrolate 300/100 μg | Change From Baseline in QTc (Fridericia's Formula) at Day 7 | 30 minutes | -0.9 milliseconds | Standard Error 1.74 |
| Indacaterol/Glycopyrrolate 300/100 μg | Change From Baseline in QTc (Fridericia's Formula) at Day 7 | 2 hours | -1.2 milliseconds | Standard Error 1.98 |
| Indacaterol/Glycopyrrolate 150/100 μg | Change From Baseline in QTc (Fridericia's Formula) at Day 7 | 30 minutes | 0.5 milliseconds | Standard Error 1.78 |
| Indacaterol/Glycopyrrolate 150/100 μg | Change From Baseline in QTc (Fridericia's Formula) at Day 7 | 2 hours | 1.6 milliseconds | Standard Error 2.02 |
| Indacaterol 300 μg | Change From Baseline in QTc (Fridericia's Formula) at Day 7 | 2 hours | -1.6 milliseconds | Standard Error 2 |
| Indacaterol 300 μg | Change From Baseline in QTc (Fridericia's Formula) at Day 7 | 30 minutes | -1.3 milliseconds | Standard Error 1.79 |
| Placebo | Change From Baseline in QTc (Fridericia's Formula) at Day 7 | 30 minutes | -2.2 milliseconds | Standard Error 1.7 |
| Placebo | Change From Baseline in QTc (Fridericia's Formula) at Day 7 | 2 hours | -2.8 milliseconds | Standard Error 1.94 |
Secondary
Trough Forced Expiratory Volume in 1 Second (FEV1) at Day 1 and Day 14
Spirometry testing was performed in accordance with American Thoracic Society standards. Trough FEV1 was defined as the mean of two measurements at 23 hours 15 minutes and 23 hour 45 minutes post dosing. Baseline is defined as the mean of the two values taken at 45 minutes and 15 minutes prior to dosing at day 1. Least square means are based on the analysis of covariance: response variable=center + treatment + baseline value + Forced Expiratory Volume in one second (FEV1) before inhalation of salbutamol/albuterol + FEV1 30 minutes post inhalation of salbutamol/albuterol.
Time frame: Day 1, Day 14
Population: Intent-to-treat Population includes all randomized patients. Any spirometric data collected less than six hours after rescue medication use was regarded as missing.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Indacaterol/Glycopyrrolate 600/100 μg | Trough Forced Expiratory Volume in 1 Second (FEV1) at Day 1 and Day 14 | Day 1 | 1.59 Liters | Standard Error 0.024 |
| Indacaterol/Glycopyrrolate 600/100 μg | Trough Forced Expiratory Volume in 1 Second (FEV1) at Day 1 and Day 14 | Day 14 | 1.61 Liters | Standard Error 0.027 |
| Indacaterol/Glycopyrrolate 300/100 μg | Trough Forced Expiratory Volume in 1 Second (FEV1) at Day 1 and Day 14 | Day 1 | 1.51 Liters | Standard Error 0.023 |
| Indacaterol/Glycopyrrolate 300/100 μg | Trough Forced Expiratory Volume in 1 Second (FEV1) at Day 1 and Day 14 | Day 14 | 1.52 Liters | Standard Error 0.025 |
| Indacaterol/Glycopyrrolate 150/100 μg | Trough Forced Expiratory Volume in 1 Second (FEV1) at Day 1 and Day 14 | Day 1 | 1.50 Liters | Standard Error 0.022 |
| Indacaterol/Glycopyrrolate 150/100 μg | Trough Forced Expiratory Volume in 1 Second (FEV1) at Day 1 and Day 14 | Day 14 | 1.50 Liters | Standard Error 0.026 |
| Indacaterol 300 μg | Trough Forced Expiratory Volume in 1 Second (FEV1) at Day 1 and Day 14 | Day 14 | 1.46 Liters | Standard Error 0.025 |
| Indacaterol 300 μg | Trough Forced Expiratory Volume in 1 Second (FEV1) at Day 1 and Day 14 | Day 1 | 1.44 Liters | Standard Error 0.023 |
| Placebo | Trough Forced Expiratory Volume in 1 Second (FEV1) at Day 1 and Day 14 | Day 1 | 1.27 Liters | Standard Error 0.022 |
| Placebo | Trough Forced Expiratory Volume in 1 Second (FEV1) at Day 1 and Day 14 | Day 14 | 1.31 Liters | Standard Error 0.024 |
Secondary
Trough Forced Vital Capacity (FVC) at Day 1 and Day 14
Spirometry testing was performed in accordance with American Thoracic Society standards. Trough FVC was defined as the mean of two measurements at 23 hours 15 minutes and the 23 hours 45 minutes post dosing. Baseline was defined as the mean of the two values taken at 45 minutes and 15 minutes prior to dosing at day 1. Analysis of covariance: FVC parameter = center + treatment + baseline FVC + FEV1 before inhalation of salbutamol/albuterol + FEV1 30 min after inhalation of salbutamol/albuterol + error.
Time frame: Day 1 and Day 14
Population: Participants from the Intent-to-treat Population (all randomized patients) with data available at the given time-point. Any spirometric data collected less than six hours after rescue medication use was regarded as missing.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Indacaterol/Glycopyrrolate 600/100 μg | Trough Forced Vital Capacity (FVC) at Day 1 and Day 14 | Day 1 | 3.151 Liters | Standard Error 0.0437 |
| Indacaterol/Glycopyrrolate 600/100 μg | Trough Forced Vital Capacity (FVC) at Day 1 and Day 14 | Day 14 (n=42, 45, 44, 48, 47) | 3.134 Liters | Standard Error 0.0469 |
| Indacaterol/Glycopyrrolate 300/100 μg | Trough Forced Vital Capacity (FVC) at Day 1 and Day 14 | Day 1 | 3.029 Liters | Standard Error 0.0421 |
| Indacaterol/Glycopyrrolate 300/100 μg | Trough Forced Vital Capacity (FVC) at Day 1 and Day 14 | Day 14 (n=42, 45, 44, 48, 47) | 3.042 Liters | Standard Error 0.0446 |
| Indacaterol/Glycopyrrolate 150/100 μg | Trough Forced Vital Capacity (FVC) at Day 1 and Day 14 | Day 1 | 3.000 Liters | Standard Error 0.0403 |
| Indacaterol/Glycopyrrolate 150/100 μg | Trough Forced Vital Capacity (FVC) at Day 1 and Day 14 | Day 14 (n=42, 45, 44, 48, 47) | 2.952 Liters | Standard Error 0.0455 |
| Indacaterol 300 μg | Trough Forced Vital Capacity (FVC) at Day 1 and Day 14 | Day 14 (n=42, 45, 44, 48, 47) | 2.901 Liters | Standard Error 0.0442 |
| Indacaterol 300 μg | Trough Forced Vital Capacity (FVC) at Day 1 and Day 14 | Day 1 | 2.924 Liters | Standard Error 0.0419 |
| Placebo | Trough Forced Vital Capacity (FVC) at Day 1 and Day 14 | Day 1 | 2.634 Liters | Standard Error 0.0402 |
| Placebo | Trough Forced Vital Capacity (FVC) at Day 1 and Day 14 | Day 14 (n=42, 45, 44, 48, 47) | 2.726 Liters | Standard Error 0.0424 |