Trial Outcomes & Findings for QVA149 Versus Fluticasone/Salmeterol in Patients With Chronic Obstructive Pulmonary Disease (COPD) (NCT NCT01315249)

NCT ID: NCT01315249

Last Updated: 2013-08-09

Results Overview

Forced Expiratory Volume in one second (FEV1) was calculated as the volume of air forcibly exhaled in one second as measured by a spirometer. FEV1 was normalized by 12 hours (divided by time). This outcome measures absolute values at week 26. Results are obtained from linear mixed model.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 523 participants
• Primary outcome timeframe: Week 26
• Results posted on: 2013-08-09

Participant Flow

All eligible patients were randomized to one of the 2 arms in a 1:1 ratio for 26 weeks of treatment.

A total of 523 patients were randomized. A total of 522 patients (99.8%) were included in the Full analysis Set (FAS) and Safety set. One patient was excluded who was randomized in error and did not receive study medication.

Participant milestones

Measure	QVA149 Participants received indacaterol and glycopyrronium (QVA149) and placebo to fluticasone/salmeterol.	Fluticasone/Salmeterol Participants received fluticasone/salmeterol and placebo to indacaterol and glycopyrronium (QVA149).
Overall Study STARTED	259	264
Overall Study COMPLETED	215	217
Overall Study NOT COMPLETED	44	47

Reasons for withdrawal

Measure	QVA149 Participants received indacaterol and glycopyrronium (QVA149) and placebo to fluticasone/salmeterol.	Fluticasone/Salmeterol Participants received fluticasone/salmeterol and placebo to indacaterol and glycopyrronium (QVA149).
Overall Study Adverse Event	22	26
Overall Study Withdrawal by Subject	11	10
Overall Study Protocol Violation	8	5
Overall Study Abnormal test results	1	2
Overall Study Administrative problems	1	0
Overall Study inability to use device	1	0
Overall Study Lack of Efficacy	0	1
Overall Study Lost to Follow-up	0	2
Overall Study Death	0	1

Baseline Characteristics

QVA149 Versus Fluticasone/Salmeterol in Patients With Chronic Obstructive Pulmonary Disease (COPD)

Baseline characteristics by cohort

Measure	QVA149 n=258 Participants Participants received indacaterol and glycopyrronium (QVA149) and placebo to fluticasone/salmeterol.	Fluticasone/Salmeterol n=264 Participants Participants received fluticasone/salmeterol and placebo to indacaterol and glycopyrronium (QVA149).	Total n=522 Participants Total of all reporting groups
Age Continuous	63.2 years STANDARD_DEVIATION 8.16 • n=5 Participants	63.4 years STANDARD_DEVIATION 7.71 • n=7 Participants	63.3 years STANDARD_DEVIATION 7.93 • n=5 Participants
Sex: Female, Male Female	77 Participants n=5 Participants	75 Participants n=7 Participants	152 Participants n=5 Participants
Sex: Female, Male Male	181 Participants n=5 Participants	189 Participants n=7 Participants	370 Participants n=5 Participants

PRIMARY outcome

Timeframe: Week 26

Population: The Full Analysis Set (FAS) included all randomized patients who received at least one dose of study drug. FAS were used to analyze all efficacy endpoints, unless otherwise stated. Following the intention-to-treat principle, patients in the FAS were analyzed according to the treatment they were randomized to.

Forced Expiratory Volume in one second (FEV1) was calculated as the volume of air forcibly exhaled in one second as measured by a spirometer. FEV1 was normalized by 12 hours (divided by time). This outcome measures absolute values at week 26. Results are obtained from linear mixed model.

Outcome measures

Measure	QVA149 n=212 Participants Participants received indacaterol and glycopyrronium (QVA149) and placebo to fluticasone/salmeterol.	Fluticasone/Salmeterol n=216 Participants Participants received fluticasone/salmeterol and placebo to indacaterol and glycopyrronium (QVA149).
Forced Expiratory Volume in 1 Second Area Under the Curve (FEV1 AUC) 0-12	1.69 liters Standard Error 0.027	1.56 liters Standard Error 0.026

SECONDARY outcome

Timeframe: Week 12

Population: The Full Analysis Set (FAS) includes all randomized patients who received at least one dose of study drug. FAS were used to analyze all efficacy endpoints, unless otherwise stated. Following the intention-to-treat principle, patients in the FAS were analyzed according to the treatment they were randomized to.

Standardized Forced Expiratory Volume in 1 Second (FEV1) was measured with spirometry conducted according to internationally accepted standards. Measurements were made between 0 and 12 hours after treatment. FEV1 was normalized by 12 hours (divided by time). This outcome measures absolute values at week 12. Results are obtained from linear mixed model.

Outcome measures

Measure	QVA149 n=255 Participants Participants received indacaterol and glycopyrronium (QVA149) and placebo to fluticasone/salmeterol.	Fluticasone/Salmeterol n=261 Participants Participants received fluticasone/salmeterol and placebo to indacaterol and glycopyrronium (QVA149).
Standardized Forced Expiratory Volume in 1 Second Area Under the Curve (FEV1 AUC) 0-12 Hours	1.71 liters Standard Error 0.023	1.59 liters Standard Error 0.022

SECONDARY outcome

Timeframe: -45 min, -15 min predose; 5 min, 30 min, 1 hr, 2hr, 4 hr, 8 hr, 12 hr post-dose on week 12

Population: The Full Analysis Set (FAS) includes all randomized patients who received at least one dose of study drug. FAS were used to analyze all efficacy endpoints, unless otherwise stated. Following the intention-to-treat principle, patients in the FAS were analyzed according to the treatment they were randomized to.

Forced Vital Capacity (FVC) is the amount of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. FVC was assessed via spirometry. A positive change from baseline in FVC indicates improvement in lung function.

This outcome measures absolute values at -45 min, -15 min predose; 5 min, 30 min, 1 hr, 2hr, 4 hr, 8 hr, 12 hr post-dose week 12. Results are obtained from linear mixed model.

Outcome measures

Measure	QVA149 n=230 Participants Participants received indacaterol and glycopyrronium (QVA149) and placebo to fluticasone/salmeterol.	Fluticasone/Salmeterol n=237 Participants Participants received fluticasone/salmeterol and placebo to indacaterol and glycopyrronium (QVA149).
Forced Vital Capacity at All-time Points (Week 12) -45 minutes (n=230 QVA149; 237 flut/salm)	3.37 liters Standard Error 0.046	3.16 liters Standard Error 0.044
Forced Vital Capacity at All-time Points (Week 12) -15 minutes (n=228 QVA149; 235 flut/salm)	3.37 liters Standard Error 0.047	3.17 liters Standard Error 0.045
Forced Vital Capacity at All-time Points (Week 12) 5 minutes (n=229 QVA149; 236 flut/salm)	3.44 liters Standard Error 0.048	3.20 liters Standard Error 0.046
Forced Vital Capacity at All-time Points (Week 12) 30 minutes (n=229 QVA149; 235 flut/salm)	3.48 liters Standard Error 0.048	3.23 liters Standard Error 0.046
Forced Vital Capacity at All-time Points (Week 12) 1 hour (n=228 QVA149; 236 flut/salm)	3.49 liters Standard Error 0.049	3.26 liters Standard Error 0.047
Forced Vital Capacity at All-time Points (Week 12) 2 hours (n=229 QVA149; 237 flut/salm)	3.54 liters Standard Error 0.048	3.31 liters Standard Error 0.046
Forced Vital Capacity at All-time Points (Week 12) 4 hours (n=228 QVA149; 237 flut/salm)	3.49 liters Standard Error 0.050	3.33 liters Standard Error 0.048
Forced Vital Capacity at All-time Points (Week 12) 8 hours (n=228 QVA149; 237 flut/salm)	3.46 liters Standard Error 0.048	3.27 liters Standard Error 0.046
Forced Vital Capacity at All-time Points (Week 12) 12 hours (n=228 QVA149; 236 flut/salm)	3.45 liters Standard Error 0.050	3.26 liters Standard Error 0.049

SECONDARY outcome

Timeframe: -45 min, -15 min predose; 5 min, 30 min, 1 hr, 2hr, 4 hr, 8 hr, 12 hr post-dose on week 26

Population: The Full Analysis Set (FAS) includes all randomized patients who received at least one dose of study drug. FAS were used to analyze all efficacy endpoints, unless otherwise stated. Following the intention-to-treat principle, patients in the FAS were analyzed according to the treatment they were randomized to.

Forced Vital Capacity (FVC) is the amount of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. FVC was assessed via spirometry. A positive change from baseline in FVC indicates improvement in lung function.

This outcome measures absolute values at -45 min, -15 min predose; 5 min, 30 min, 1 hr, 2hr, 4 hr, 8 hr, 12 hr post-dose on week 26. Results are obtained from linear mixed model.

Outcome measures

Measure	QVA149 n=213 Participants Participants received indacaterol and glycopyrronium (QVA149) and placebo to fluticasone/salmeterol.	Fluticasone/Salmeterol n=216 Participants Participants received fluticasone/salmeterol and placebo to indacaterol and glycopyrronium (QVA149).
Forced Vital Capacity at All-time Points (Week 26) -45 minutes (n=213 QVA149; 216 flut/salm)	3.32 liters Standard Error 0.047	3.13 liters Standard Error 0.045
Forced Vital Capacity at All-time Points (Week 26) -15 minutes (n=213 QVA149; 215 flut/salm)	3.33 liters Standard Error 0.044	3.12 liters Standard Error 0.043
Forced Vital Capacity at All-time Points (Week 26) 5 minutes (n=212 QVA149; 215 flut/salm)	3.42 liters Standard Error 0.051	3.17 liters Standard Error 0.049
Forced Vital Capacity at All-time Points (Week 26) 30 minutes (n=212 QVA149; 214 flut/salm)	3.47 liters Standard Error 0.053	3.23 liters Standard Error 0.051
Forced Vital Capacity at All-time Points (Week 26) 1 hour (n=212 QVA149; 216 flut/salm)	3.50 liters Standard Error 0.051	3.23 liters Standard Error 0.049
Forced Vital Capacity at All-time Points (Week 26) 2 hours (n=212 QVA149; 216 flut/salm)	3.51 liters Standard Error 0.051	3.29 liters Standard Error 0.049
Forced Vital Capacity at All-time Points (Week 26) 4 hours (n=212 QVA149; 215 flut/salm)	3.45 liters Standard Error 0.053	3.28 liters Standard Error 0.050
Forced Vital Capacity at All-time Points (Week 26) 8 hours (n=212 QVA149; 216 flut/salm)	3.40 liters Standard Error 0.053	3.21 liters Standard Error 0.050
Forced Vital Capacity at All-time Points (Week 26) 12 hours (n=211 QVA149; 213 flut/salm)	3.40 liters Standard Error 0.053	3.18 liters Standard Error 0.051

SECONDARY outcome

Timeframe: 12 weeks and 26 weeks

Population: The Full Analysis Set (FAS) includes all randomized patients who received at least one dose of study drug. FAS were used to analyze all efficacy endpoints, unless otherwise stated. Following the intention-to-treat principle, patients in the FAS were analyzed according to the treatment they were randomized to.

Transition Dyspnea Index (TDI) captures changes from baseline. The TDI score is based on three domains with each domain scored from -3 (major deterioration) to +3 (major improvement), to give an overall score of -9 to +9, a negative score indicating a deterioration from baseline. A TDI focal score of 1 is considered to be a clinically significant improvement.

Outcome measures

Measure	QVA149 n=224 Participants Participants received indacaterol and glycopyrronium (QVA149) and placebo to fluticasone/salmeterol.	Fluticasone/Salmeterol n=236 Participants Participants received fluticasone/salmeterol and placebo to indacaterol and glycopyrronium (QVA149).
Focal Score of the Transitional Dyspnea Index (TDI) 12 weeks (n=224 QVA149; 236 flut/salm)	2.03 units on a scale Standard Error 0.388	1.45 units on a scale Standard Error 0.374
Focal Score of the Transitional Dyspnea Index (TDI) 26 weeks (n=212 QVA149; 213 flut/salm)	2.36 units on a scale Standard Error 0.388	1.60 units on a scale Standard Error 0.376

SECONDARY outcome

Timeframe: 12 weeks and 26 weeks

Population: The Full Analysis Set (FAS) includes all randomized patients who received at least one dose of study drug. FAS were used to analyze all efficacy endpoints, unless otherwise stated. Following the intention-to-treat principle, patients in the FAS were analyzed according to the treatment they were randomized to.

The total score of the St. George's Respiratory Questionnaire (SGRQ-C) is a health related quality of life questionnaire consisting of 51 items in three components: symptoms, activity, and impacts. The lowest possible value is zero and the highest 100. Higher values correspond to greater impairment in quality of life.

Outcome measures

Measure	QVA149 n=230 Participants Participants received indacaterol and glycopyrronium (QVA149) and placebo to fluticasone/salmeterol.	Fluticasone/Salmeterol n=238 Participants Participants received fluticasone/salmeterol and placebo to indacaterol and glycopyrronium (QVA149).
Total Score of the St. George's Respiratory Questionnaire (SGRQ-C) 12 weeks (n=230 QVA149; 238 flut/salm)	36.74 units on a scale Standard Error 1.175	36.03 units on a scale Standard Error 1.132
Total Score of the St. George's Respiratory Questionnaire (SGRQ-C) 26 weeks (n=211 QVA149; 216 flut/salm)	35.45 units on a scale Standard Error 1.448	36.68 units on a scale Standard Error 1.386

SECONDARY outcome

Timeframe: Baseline, 12 weeks and 26 weeks

Population: The Full Analysis Set (FAS) includes all randomized patients who received at least one dose of study drug. FAS were used to analyze all efficacy endpoints, unless otherwise stated. Following the intention-to-treat principle, patients in the FAS were analyzed according to the treatment they were randomized to.

Participants maintained a diary to record the daily number of puffs of rescue medication used to treat COPD symptoms.

Outcome measures

Measure	QVA149 n=253 Participants Participants received indacaterol and glycopyrronium (QVA149) and placebo to fluticasone/salmeterol.	Fluticasone/Salmeterol n=259 Participants Participants received fluticasone/salmeterol and placebo to indacaterol and glycopyrronium (QVA149).
Mean Change From Baseline in Daily Number of Puffs of Rescue Medication Weeks 1 to12	-2.18 puffs Standard Error 0.187	-1.90 puffs Standard Error 0.184
Mean Change From Baseline in Daily Number of Puffs of Rescue Medication Weeks 1 to 26	-2.32 puffs Standard Error 0.194	-1.93 puffs Standard Error 0.191

SECONDARY outcome

Timeframe: 12 weeks and 26 weeks

Population: The Full Analysis Set (FAS) includes all randomized patients who received at least one dose of study drug. FAS were used to analyze all efficacy endpoints, unless otherwise stated. Following the intention-to-treat principle, patients in the FAS were analyzed according to the treatment they were randomized to.

Participants maintained an ediary to record daily symptom scores (AM and PM) over 12 weeks and 26 weeks of treatment. This analysis compares the mean symptom scores over 12 weeks and 26 weeks compared to baseline. The diary records morning and evening daily clinical symptoms including cough, wheezing, shortness of breath, sputum volume, sputum purulence, night time awakenings and rescue medication use.

Scale ranges: ranges are 0 to 3 with varying scale descriptions that pertain to the question being asked.

0 is the minimum score = "none" or "No symptoms" or "never" or "No"

1. = mild, a little

2. = moderate

3. = severe For the scale range provided, high values represent a worse outcome.

Outcome measures

Measure	QVA149 n=253 Participants Participants received indacaterol and glycopyrronium (QVA149) and placebo to fluticasone/salmeterol.	Fluticasone/Salmeterol n=259 Participants Participants received fluticasone/salmeterol and placebo to indacaterol and glycopyrronium (QVA149).
Change From Baseline in Symptom Scores Reported Using the Ediary Weeks 1-12	-1.08 units on a scale Standard Error 0.135	-1.17 units on a scale Standard Error 0.133
Change From Baseline in Symptom Scores Reported Using the Ediary Weeks 1-26	-1.28 units on a scale Standard Error 0.140	-1.24 units on a scale Standard Error 0.138

SECONDARY outcome

Timeframe: 12 weeks

Population: Inspiratory capacity was measured for a subset of patients QVA149 group: (78 patients (30.2%)) at baseline and 49-73 patients contributing observations at post-baseline visits. flut/salm group: (86 patients (32.6%)) at baseline and 60-79 patients contributing observations at post-baseline visits.

After 12 weeks of treatment, Inspiratory Capacity (IC) was measured via spirometry, conducted according to internationally accepted standards. The mean of 3 acceptable measurements was calculated and reported in liters.

Outcome measures

Measure	QVA149 n=58 Participants Participants received indacaterol and glycopyrronium (QVA149) and placebo to fluticasone/salmeterol.	Fluticasone/Salmeterol n=72 Participants Participants received fluticasone/salmeterol and placebo to indacaterol and glycopyrronium (QVA149).
Inspiratory Capacity (IC) at All-time Points (12 Weeks) -20 minutes (n=51 QVA149; 65 flut/salm)	2.39 Liters Standard Error 0.081	2.31 Liters Standard Error 0.073
Inspiratory Capacity (IC) at All-time Points (12 Weeks) 25 minutes (n=56 QVA149; 71 flut/salm)	2.55 Liters Standard Error 0.075	2.42 Liters Standard Error 0.068
Inspiratory Capacity (IC) at All-time Points (12 Weeks) 1 hour (n=59 QVA149; 68 flut/salm)	2.54 Liters Standard Error 0.079	2.43 Liters Standard Error 0.072
Inspiratory Capacity (IC) at All-time Points (12 Weeks) 3 hours (n=54 QVA149; 67 flut/salm)	2.52 Liters Standard Error 0.086	2.45 Liters Standard Error 0.079
Inspiratory Capacity (IC) at All-time Points (12 Weeks) 7 hours (n=58 QVA149; 67 flut/salm)	2.42 Liters Standard Error 0.080	2.41 Liters Standard Error 0.073
Inspiratory Capacity (IC) at All-time Points (12 Weeks) 11 hours (n=49 QVA149; 72 flut/salm)	2.40 Liters Standard Error 0.079	2.34 Liters Standard Error 0.070

SECONDARY outcome

Timeframe: 26 weeks

Population: Inspiratory capacity was measured for a subset of patients QVA149 group: (78 patients (30.2%)) at baseline and 49-73 patients contributing observations at post-baseline visits. flut/salm group: (86 patients (32.6%)) at baseline and 60-79 patients contributing observations at post-baseline visits.

After 26 weeks of treatment, Inspiratory Capacity (IC) was measured via spirometry, conducted according to internationally accepted standards. The mean of 3 acceptable measurements was calculated and reported in liters.

Outcome measures

Measure	QVA149 n=58 Participants Participants received indacaterol and glycopyrronium (QVA149) and placebo to fluticasone/salmeterol.	Fluticasone/Salmeterol n=66 Participants Participants received fluticasone/salmeterol and placebo to indacaterol and glycopyrronium (QVA149).
Inspiratory Capacity (IC) at All-time Points (26 Weeks) -20 minutes (n=53 QVA149; 63 flut/salm)	2.25 Liters Standard Error 0.079	2.22 Liters Standard Error 0.071
Inspiratory Capacity (IC) at All-time Points (26 Weeks) 25 minutes (n=58 QVA149; 63 flut/salm)	2.41 Liters Standard Error 0.088	2.34 Liters Standard Error 0.080
Inspiratory Capacity (IC) at All-time Points (26 Weeks) 1 hour (n=53 QVA149; 63 flut/salm)	2.38 Liters Standard Error 0.087	2.35 Liters Standard Error 0.079
Inspiratory Capacity (IC) at All-time Points (26 Weeks) 3 hours (n=52 QVA149; 60 flut/salm)	2.33 Liters Standard Error 0.090	2.32 Liters Standard Error 0.080
Inspiratory Capacity (IC) at All-time Points (26 Weeks) 7 hours (n=56 QVA149; 61 flut/salm)	2.40 Liters Standard Error 0.82	2.30 Liters Standard Error 0.075
Inspiratory Capacity (IC) at All-time Points (26 Weeks) 11 hours (n=57 QVA149; 66 flut/salm)	2.37 Liters Standard Error 0.084	2.27 Liters Standard Error 0.075

SECONDARY outcome

Timeframe: 26 weeks

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

The assessment of safety was based on Adverse Events. A summary of adverse events is presented with this outcome, additional details are provided in Adverse Events Section.

Outcome measures

Measure	QVA149 n=258 Participants Participants received indacaterol and glycopyrronium (QVA149) and placebo to fluticasone/salmeterol.	Fluticasone/Salmeterol n=264 Participants Participants received fluticasone/salmeterol and placebo to indacaterol and glycopyrronium (QVA149).
Number of Participants With Adverse Events Any Adverse Event	143 participants	159 participants
Number of Participants With Adverse Events Death	0 participants	1 participants
Number of Participants With Adverse Events Serious Adverse Events	13 participants	14 participants
Number of Participants With Adverse Events Discontinued due to Adverse Events	22 participants	27 participants
Number of Participants With Adverse Events Discontinued due to Serious Adverse Events	5 participants	9 participants
Number of Participants With Adverse Events Discontinued due to non-Serious Adverse Events	17 participants	18 participants

Adverse Events

QVA149

Serious events: 13 serious events

Other events: 73 other events

Deaths: 0 deaths

Fluticasone/Salmeterol

Serious events: 14 serious events

Other events: 82 other events

Deaths: 0 deaths

Serious adverse events

Measure	QVA149 n=258 participants at risk Participants received indacaterol and glycopyrronium (QVA149) and placebo to fluticasone/salmeterol.	Fluticasone/Salmeterol n=264 participants at risk Participants received fluticasone/salmeterol and placebo to indacaterol and glycopyrronium (QVA149).
Cardiac disorders Acute coronary syndrome	0.00% 0/258	0.38% 1/264
Cardiac disorders Acute myocardial infarction	0.39% 1/258	0.00% 0/264
Cardiac disorders Angina pectoris	0.39% 1/258	0.00% 0/264
Cardiac disorders Atrial fibrillation	0.39% 1/258	0.00% 0/264
Cardiac disorders Coronary artery stenosis	0.39% 1/258	0.00% 0/264
Gastrointestinal disorders Dyspepsia	0.39% 1/258	0.00% 0/264
Gastrointestinal disorders Dysphagia	0.39% 1/258	0.00% 0/264
Infections and infestations Abscess limb	0.00% 0/258	0.38% 1/264
Infections and infestations Bronchitis	0.00% 0/258	0.38% 1/264
Infections and infestations Nasopharyngitis	0.00% 0/258	0.38% 1/264
Infections and infestations Pneumonia	0.00% 0/258	0.76% 2/264
Injury, poisoning and procedural complications Contusion	0.39% 1/258	0.00% 0/264
Metabolism and nutrition disorders Diabetes mellitus	0.39% 1/258	0.00% 0/264
Musculoskeletal and connective tissue disorders Myopathy	0.39% 1/258	0.00% 0/264
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon cancer	0.00% 0/258	0.38% 1/264
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung adenocarcinoma	0.00% 0/258	0.38% 1/264
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Oesophageal carcinoma	0.39% 1/258	0.00% 0/264
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Rectal cancer	0.39% 1/258	0.00% 0/264
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Small cell lung cancer stage unspecified	0.00% 0/258	0.38% 1/264
Nervous system disorders Carotid artery occlusion	0.00% 0/258	0.38% 1/264
Nervous system disorders Carotid artery stenosis	0.39% 1/258	0.00% 0/264
Nervous system disorders Ischaemic stroke	0.00% 0/258	0.38% 1/264
Reproductive system and breast disorders Benign prostatic hyperplasia	0.39% 1/258	0.00% 0/264
Reproductive system and breast disorders Epididymitis	0.00% 0/258	0.38% 1/264
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.39% 1/258	0.00% 0/264
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.39% 1/258	1.1% 3/264
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.39% 1/258	0.00% 0/264
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.39% 1/258	0.38% 1/264
Skin and subcutaneous tissue disorders Skin ulcer	0.00% 0/258	0.38% 1/264
Vascular disorders Peripheral artery aneurysm	0.00% 0/258	0.38% 1/264
Vascular disorders Venous insufficiency	0.00% 0/258	0.38% 1/264
Vascular disorders Venous thrombosis limb	0.39% 1/258	0.00% 0/264

Other adverse events

Measure	QVA149 n=258 participants at risk Participants received indacaterol and glycopyrronium (QVA149) and placebo to fluticasone/salmeterol.	Fluticasone/Salmeterol n=264 participants at risk Participants received fluticasone/salmeterol and placebo to indacaterol and glycopyrronium (QVA149).
Infections and infestations Nasopharyngitis	14.3% 37/258	11.0% 29/264
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	17.1% 44/258	22.7% 60/264

Additional Information

Study Director

Novartis

Phone: 41 61 324 1111

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