Trial Outcomes & Findings for Safety and Tolerability of QVA149 (Indacaterol/Glycopyrrolate) Compared to Placebo and to Indacaterol in Patients With Moderate to Severe Stable Chronic Obstructive Pulmonary Disease (COPD) (NCT NCT00558285)

NCT ID: NCT00558285

Last Updated: 2012-11-30

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 257 participants
• Primary outcome timeframe: Baseline, Day 14
• Results posted on: 2012-11-30

Participant Flow

Participant milestones

Measure	Indacaterol/Glycopyrrolate 600 μg/100 μg Two capsules indacaterol/glycopyrrolate 300 μg/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.	Indacaterol/Glycopyrrolate 300 μg/100 μg One capsule indacaterol/glycopyrrolate 300 μg/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.	Indacaterol/Glycopyrrolate 150 μg/100 μg One capsule indacaterol/glycopyrrolate 150 μg/50 μg and one capsule 50μg 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.	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.	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.
Overall Study STARTED	50	51	51	52	53
Overall Study Safety: Received Study Drug	49	51	51	51	53
Overall Study COMPLETED	44	48	46	48	49
Overall Study NOT COMPLETED	6	3	5	4	4

Reasons for withdrawal

Measure	Indacaterol/Glycopyrrolate 600 μg/100 μg Two capsules indacaterol/glycopyrrolate 300 μg/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.	Indacaterol/Glycopyrrolate 300 μg/100 μg One capsule indacaterol/glycopyrrolate 300 μg/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.	Indacaterol/Glycopyrrolate 150 μg/100 μg One capsule indacaterol/glycopyrrolate 150 μg/50 μg and one capsule 50μg 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.	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.	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.
Overall Study Adverse Event	1	1	4	1	2
Overall Study Abnormal test procedure result(s)	1	0	0	0	0
Overall Study Subject withdrew consent	2	0	1	1	1
Overall Study Lost to Follow-up	1	1	0	0	0
Overall Study Administrative problems	0	0	0	1	1
Overall Study Protocol deviation	1	1	0	1	0

Baseline Characteristics

Safety and Tolerability of QVA149 (Indacaterol/Glycopyrrolate) Compared to Placebo and to Indacaterol in Patients With Moderate to Severe Stable Chronic Obstructive Pulmonary Disease (COPD)

Baseline characteristics by cohort

Measure	Indacaterol/Glycopyrrolate 600/100 μg n=49 Participants 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.	Indacaterol/Glycopyrrolate 300/100 μg n=51 Participants 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.	Indacaterol/Glycopyrrolate 150/100 μg n=51 Participants 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.	Indacaterol 300 μg n=51 Participants 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.	Placebo n=53 Participants 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.	Total n=255 Participants Total of all reporting groups
Age Continuous	65.7 years STANDARD_DEVIATION 9.34 • n=5 Participants	63.7 years STANDARD_DEVIATION 8.94 • n=7 Participants	60.9 years STANDARD_DEVIATION 8.58 • n=5 Participants	64.5 years STANDARD_DEVIATION 9.75 • n=4 Participants	64.3 years STANDARD_DEVIATION 8.95 • n=21 Participants	63.8 years STANDARD_DEVIATION 9.19 • n=8 Participants
Sex: Female, Male Female	11 Participants n=5 Participants	10 Participants n=7 Participants	15 Participants n=5 Participants	10 Participants n=4 Participants	14 Participants n=21 Participants	60 Participants n=8 Participants
Sex: Female, Male Male	38 Participants n=5 Participants	41 Participants n=7 Participants	36 Participants n=5 Participants	41 Participants n=4 Participants	39 Participants n=21 Participants	195 Participants n=8 Participants

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Indacaterol/Glycopyrrolate 600/100 μg n=39 Participants 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.	Indacaterol/Glycopyrrolate 300/100 μg n=45 Participants 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.	Indacaterol/Glycopyrrolate 150/100 μg n=40 Participants 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.	Indacaterol 300 μg n=42 Participants 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.	Placebo n=45 Participants 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.
Change From Baseline in Mean 24 Hour Heart Rate at Day 14	-0.113 beats per minute Standard Error 0.9967	0.787 beats per minute Standard Error 0.8975	-0.230 beats per minute Standard Error 0.9567	0.240 beats per minute Standard Error 0.9373	0.170 beats per minute Standard Error 0.8760

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Indacaterol/Glycopyrrolate 600/100 μg n=45 Participants 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.	Indacaterol/Glycopyrrolate 300/100 μg n=46 Participants 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.	Indacaterol/Glycopyrrolate 150/100 μg n=47 Participants 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.	Indacaterol 300 μg n=48 Participants 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.	Placebo n=47 Participants 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.
Change From Baseline in Mean 24 Hour Heart Rate at Day 1	-2.877 beats per minute Standard Error 0.8790	-2.770 beats per minute Standard Error 0.8244	-0.547 beats per minute Standard Error 0.8208	-1.849 beats per minute Standard Error 0.8211	-0.329 beats per minute Standard Error 0.8181

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Indacaterol/Glycopyrrolate 600/100 μg n=50 Participants 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.	Indacaterol/Glycopyrrolate 300/100 μg n=51 Participants 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.	Indacaterol/Glycopyrrolate 150/100 μg n=51 Participants 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.	Indacaterol 300 μg n=52 Participants 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.	Placebo n=53 Participants 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.
Trough Forced Expiratory Volume in 1 Second (FEV1) at Day 1 and Day 14 Day 14	1.61 Liters Standard Error 0.027	1.52 Liters Standard Error 0.025	1.50 Liters Standard Error 0.026	1.46 Liters Standard Error 0.025	1.31 Liters Standard Error 0.024
Trough Forced Expiratory Volume in 1 Second (FEV1) at Day 1 and Day 14 Day 1	1.59 Liters Standard Error 0.024	1.51 Liters Standard Error 0.023	1.50 Liters Standard Error 0.022	1.44 Liters Standard Error 0.023	1.27 Liters Standard Error 0.022

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Indacaterol/Glycopyrrolate 600/100 μg n=48 Participants 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.	Indacaterol/Glycopyrrolate 300/100 μg n=48 Participants 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.	Indacaterol/Glycopyrrolate 150/100 μg n=51 Participants 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.	Indacaterol 300 μg n=49 Participants 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.	Placebo n=52 Participants 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.
Trough Forced Vital Capacity (FVC) at Day 1 and Day 14 Day 1	3.151 Liters Standard Error 0.0437	3.029 Liters Standard Error 0.0421	3.000 Liters Standard Error 0.0403	2.924 Liters Standard Error 0.0419	2.634 Liters Standard Error 0.0402
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	3.042 Liters Standard Error 0.0446	2.952 Liters Standard Error 0.0455	2.901 Liters Standard Error 0.0442	2.726 Liters Standard Error 0.0424

SECONDARY outcome

Timeframe: Baseline, Day 1

Population: Safety Population includes all patients who received at least one dose of study drug.

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.

Outcome measures

Measure	Indacaterol/Glycopyrrolate 600/100 μg n=49 Participants 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.	Indacaterol/Glycopyrrolate 300/100 μg n=51 Participants 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.	Indacaterol/Glycopyrrolate 150/100 μg n=51 Participants 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.	Indacaterol 300 μg n=51 Participants 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.	Placebo n=53 Participants 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.
Change From Baseline in QTc (Fridericia's Formula) at Day 1 30 minutes	1.6 milliseconds Standard Error 1.58	1.2 milliseconds Standard Error 1.48	1.4 milliseconds Standard Error 1.50	3.1 milliseconds Standard Error 1.47	-1.6 milliseconds Standard Error 1.44
Change From Baseline in QTc (Fridericia's Formula) at Day 1 4 hours	2.8 milliseconds Standard Error 1.67	0.5 milliseconds Standard Error 1.56	2.4 milliseconds Standard Error 1.58	1.1 milliseconds Standard Error 1.60	-2.3 milliseconds Standard Error 1.52
Change From Baseline in QTc (Fridericia's Formula) at Day 1 23 hours 45 minutes	2.7 milliseconds Standard Error 1.77	-1.7 milliseconds Standard Error 1.66	-0.1 milliseconds Standard Error 1.67	-2.1 milliseconds Standard Error 1.71	-2.3 milliseconds Standard Error 1.62

SECONDARY outcome

Timeframe: Baseline, Day 7

Population: Safety Population includes all patients who received at least one dose of study drug.

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.

Outcome measures

Measure	Indacaterol/Glycopyrrolate 600/100 μg n=49 Participants 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.	Indacaterol/Glycopyrrolate 300/100 μg n=51 Participants 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.	Indacaterol/Glycopyrrolate 150/100 μg n=51 Participants 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.	Indacaterol 300 μg n=51 Participants 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.	Placebo n=53 Participants 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.
Change From Baseline in QTc (Fridericia's Formula) at Day 7 30 minutes	4.1 milliseconds Standard Error 1.91	-0.9 milliseconds Standard Error 1.74	0.5 milliseconds Standard Error 1.78	-1.3 milliseconds Standard Error 1.79	-2.2 milliseconds Standard Error 1.70
Change From Baseline in QTc (Fridericia's Formula) at Day 7 2 hours	2.6 milliseconds Standard Error 2.17	-1.2 milliseconds Standard Error 1.98	1.6 milliseconds Standard Error 2.02	-1.6 milliseconds Standard Error 2.00	-2.8 milliseconds Standard Error 1.94

SECONDARY outcome

Timeframe: Baseline, Day 14

Population: Safety Population includes all patients who received at least one dose of study drug.

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.

Outcome measures

Measure	Indacaterol/Glycopyrrolate 600/100 μg n=49 Participants 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.	Indacaterol/Glycopyrrolate 300/100 μg n=51 Participants 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.	Indacaterol/Glycopyrrolate 150/100 μg n=51 Participants 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.	Indacaterol 300 μg n=51 Participants 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.	Placebo n=53 Participants 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.
Change From Baseline in QTc (Fridericia's Formula) at Day 14 30 minutes	2.4 milliseconds Standard Error 1.79	-0.6 milliseconds Standard Error 1.64	1.6 milliseconds Standard Error 1.70	-1.2 milliseconds Standard Error 1.69	0.2 milliseconds Standard Error 1.62
Change From Baseline in QTc (Fridericia's Formula) at Day 14 4 hours	2.8 milliseconds Standard Error 1.90	-0.1 milliseconds Standard Error 1.76	3.1 milliseconds Standard Error 1.85	-2.6 milliseconds Standard Error 1.81	-0.1 milliseconds Standard Error 1.73
Change From Baseline in QTc (Fridericia's Formula) at Day 14 23 hours 45 minutes	0.5 milliseconds Standard Error 1.94	-2.9 milliseconds Standard Error 1.81	0.4 milliseconds Standard Error 1.95	-3.6 milliseconds Standard Error 1.88	-1.6 milliseconds Standard Error 1.77

Adverse Events

Indacaterol/Glycopyrrolate 600/100 μg

Serious events: 2 serious events

Other events: 5 other events

Deaths: 0 deaths

Indacaterol/Glycopyrrolate 300/100 μg

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Indacaterol/Glycopyrrolate 150/100 μg

Serious events: 2 serious events

Other events: 10 other events

Deaths: 0 deaths

Indacaterol 300 μg

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Placebo

Serious events: 1 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Measure	Indacaterol/Glycopyrrolate 600/100 μg n=49 participants at risk 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.	Indacaterol/Glycopyrrolate 300/100 μg n=51 participants at risk 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.	Indacaterol/Glycopyrrolate 150/100 μg n=51 participants at risk 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.	Indacaterol 300 μg n=51 participants at risk 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.	Placebo n=53 participants at risk 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.
Blood and lymphatic system disorders Anaemia	0.00% 0/49	0.00% 0/51	2.0% 1/51	0.00% 0/51	0.00% 0/53
Cardiac disorders Atrial fibrillation	2.0% 1/49	0.00% 0/51	0.00% 0/51	0.00% 0/51	0.00% 0/53
Cardiac disorders Ventricular tachycardia	0.00% 0/49	0.00% 0/51	2.0% 1/51	0.00% 0/51	0.00% 0/53
Investigations Blood potassium increased	2.0% 1/49	0.00% 0/51	0.00% 0/51	0.00% 0/51	0.00% 0/53
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.00% 0/49	0.00% 0/51	0.00% 0/51	0.00% 0/51	1.9% 1/53

Other adverse events

Measure	Indacaterol/Glycopyrrolate 600/100 μg n=49 participants at risk 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.	Indacaterol/Glycopyrrolate 300/100 μg n=51 participants at risk 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.	Indacaterol/Glycopyrrolate 150/100 μg n=51 participants at risk 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.	Indacaterol 300 μg n=51 participants at risk 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.	Placebo n=53 participants at risk 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.
Gastrointestinal disorders Dry mouth	6.1% 3/49	2.0% 1/51	5.9% 3/51	0.00% 0/51	0.00% 0/53
Nervous system disorders Headache	4.1% 2/49	2.0% 1/51	3.9% 2/51	5.9% 3/51	1.9% 1/53
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.00% 0/49	3.9% 2/51	9.8% 5/51	2.0% 1/51	1.9% 1/53
Respiratory, thoracic and mediastinal disorders Cough	6.1% 3/49	3.9% 2/51	5.9% 3/51	3.9% 2/51	1.9% 1/53
Vascular disorders Hypertension	0.00% 0/49	5.9% 3/51	2.0% 1/51	2.0% 1/51	1.9% 1/53

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 862-778-8300

Results disclosure agreements

• Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.
• Publication restrictions are in place

Restriction type: OTHER