Chronic Obstructive Pulmonary Disease (COPD)
Conditions
Keywords
QVA149, indacaterol, NVA237, COPD, fluticasone/salmeterol
Brief summary
The purpose of this study is to compare the efficacy and safety/tolerability of indacaterol and glycopyrronium (QVA149) (fixed-dose combination) with fluticasone/salmeterol over a 26-week period in patients with moderate to severe COPD.
Interventions
QVA149 capsules delivered via dry powder inhaler (SDDPI), once daily.
Placebo to fluticasone/salmeterol delivered via Accuhaler® device, twice daily.
Fluticasone/salmeterol dry inhalation powder delivered via Accuhaler® device, twice daily.
DRUGPlacebo to indacaterol and glycopyrronium (QVA149)
Placebo to QVA149 delivered via dry powder inhaler (SDDPI), once daily
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Smoking history of at least 10 pack years * Diagnosis of Chronic Obstructive Pulmonary Disease (COPD) (moderate-to-severe as classified by the Global Initiative for Chronic Obstructive Lung Disease \[GOLD\] Guidelines, 2009) * Post-bronchodilator Forced Expiratory Volume in 1 second (FEV1) \>40% and \< 80% of the predicted normal value and post-bronchodilator FEV1/Forced Vital Capacity (FVC) \<70%
Exclusion criteria
* Patients who have had a COPD exacerbation that required treatment with antibiotics, systemic steroids (oral or intravenous) or hospitalization in the last year. * Patients requiring long term oxygen therapy on a daily basis for chronic hypoxemia. * Patients who have had a respiratory tract infection within 4 weeks prior to Visit 1. * Patients with concomitant pulmonary disease * Patients with a history of asthma * Any patient with lung cancer or a history of lung cancer (within last 5 years) * Patients with a history of certain cardiovascular co-morbid conditions
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Forced Expiratory Volume in 1 Second Area Under the Curve (FEV1 AUC) 0-12 | Week 26 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Forced Vital Capacity at All-time Points (Week 12) | -45 min, -15 min predose; 5 min, 30 min, 1 hr, 2hr, 4 hr, 8 hr, 12 hr post-dose on week 12 | 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. |
| Forced Vital Capacity at All-time Points (Week 26) | -45 min, -15 min predose; 5 min, 30 min, 1 hr, 2hr, 4 hr, 8 hr, 12 hr post-dose on week 26 | 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. |
| Focal Score of the Transitional Dyspnea Index (TDI) | 12 weeks and 26 weeks | 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. |
| Total Score of the St. George's Respiratory Questionnaire (SGRQ-C) | 12 weeks and 26 weeks | 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. |
| Standardized Forced Expiratory Volume in 1 Second Area Under the Curve (FEV1 AUC) 0-12 Hours | Week 12 | 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. |
| Change From Baseline in Symptom Scores Reported Using the Ediary | 12 weeks and 26 weeks | 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. |
| Inspiratory Capacity (IC) at All-time Points (12 Weeks) | 12 weeks | 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. |
| Inspiratory Capacity (IC) at All-time Points (26 Weeks) | 26 weeks | 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. |
| Number of Participants With Adverse Events | 26 weeks | 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. |
| Mean Change From Baseline in Daily Number of Puffs of Rescue Medication | Baseline, 12 weeks and 26 weeks | Participants maintained a diary to record the daily number of puffs of rescue medication used to treat COPD symptoms. |
Countries
Belgium, Czechia, Estonia, Germany, Hungary, Lithuania, Norway, South Korea, Spain
Participant flow
Recruitment details
All eligible patients were randomized to one of the 2 arms in a 1:1 ratio for 26 weeks of treatment.
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| QVA149 Participants received indacaterol and glycopyrronium (QVA149) and placebo to fluticasone/salmeterol. | 258 |
| Fluticasone/Salmeterol Participants received fluticasone/salmeterol and placebo to indacaterol and glycopyrronium (QVA149). | 264 |
| Total | 522 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Abnormal test results | 1 | 2 |
| Overall Study | Administrative problems | 1 | 0 |
| Overall Study | Adverse Event | 22 | 26 |
| Overall Study | Death | 0 | 1 |
| 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 | Protocol Violation | 8 | 5 |
| Overall Study | Withdrawal by Subject | 11 | 10 |
Baseline characteristics
| Characteristic | QVA149 | Fluticasone/Salmeterol | Total |
|---|---|---|---|
| Age Continuous | 63.2 years STANDARD_DEVIATION 8.16 | 63.4 years STANDARD_DEVIATION 7.71 | 63.3 years STANDARD_DEVIATION 7.93 |
| Sex: Female, Male Female | 77 Participants | 75 Participants | 152 Participants |
| Sex: Female, Male Male | 181 Participants | 189 Participants | 370 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 73 / 258 | 82 / 264 |
| serious Total, serious adverse events | 13 / 258 | 14 / 264 |
Outcome results
Primary
Forced Expiratory Volume in 1 Second Area Under the Curve (FEV1 AUC) 0-12
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.
Time frame: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| QVA149 | Forced Expiratory Volume in 1 Second Area Under the Curve (FEV1 AUC) 0-12 | 1.69 liters | Standard Error 0.027 |
| Fluticasone/Salmeterol | Forced Expiratory Volume in 1 Second Area Under the Curve (FEV1 AUC) 0-12 | 1.56 liters | Standard Error 0.026 |
Secondary
Change From Baseline in Symptom Scores Reported Using the Ediary
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.
Time frame: 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.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| QVA149 | Change From Baseline in Symptom Scores Reported Using the Ediary | Weeks 1-12 | -1.08 units on a scale | Standard Error 0.135 |
| QVA149 | Change From Baseline in Symptom Scores Reported Using the Ediary | Weeks 1-26 | -1.28 units on a scale | Standard Error 0.14 |
| Fluticasone/Salmeterol | Change From Baseline in Symptom Scores Reported Using the Ediary | Weeks 1-12 | -1.17 units on a scale | Standard Error 0.133 |
| Fluticasone/Salmeterol | Change From Baseline in Symptom Scores Reported Using the Ediary | Weeks 1-26 | -1.24 units on a scale | Standard Error 0.138 |
Secondary
Focal Score of the Transitional Dyspnea Index (TDI)
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.
Time frame: 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.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| 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 |
| QVA149 | 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 |
| Fluticasone/Salmeterol | Focal Score of the Transitional Dyspnea Index (TDI) | 12 weeks (n=224 QVA149; 236 flut/salm) | 1.45 units on a scale | Standard Error 0.374 |
| Fluticasone/Salmeterol | Focal Score of the Transitional Dyspnea Index (TDI) | 26 weeks (n=212 QVA149; 213 flut/salm) | 1.60 units on a scale | Standard Error 0.376 |
Secondary
Forced Vital Capacity at All-time Points (Week 12)
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.
Time frame: -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.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| QVA149 | Forced Vital Capacity at All-time Points (Week 12) | -15 minutes (n=228 QVA149; 235 flut/salm) | 3.37 liters | Standard Error 0.047 |
| QVA149 | Forced Vital Capacity at All-time Points (Week 12) | 2 hours (n=229 QVA149; 237 flut/salm) | 3.54 liters | Standard Error 0.048 |
| QVA149 | Forced Vital Capacity at All-time Points (Week 12) | 30 minutes (n=229 QVA149; 235 flut/salm) | 3.48 liters | Standard Error 0.048 |
| QVA149 | Forced Vital Capacity at All-time Points (Week 12) | 4 hours (n=228 QVA149; 237 flut/salm) | 3.49 liters | Standard Error 0.05 |
| QVA149 | Forced Vital Capacity at All-time Points (Week 12) | 5 minutes (n=229 QVA149; 236 flut/salm) | 3.44 liters | Standard Error 0.048 |
| QVA149 | Forced Vital Capacity at All-time Points (Week 12) | 8 hours (n=228 QVA149; 237 flut/salm) | 3.46 liters | Standard Error 0.048 |
| QVA149 | Forced Vital Capacity at All-time Points (Week 12) | 1 hour (n=228 QVA149; 236 flut/salm) | 3.49 liters | Standard Error 0.049 |
| QVA149 | Forced Vital Capacity at All-time Points (Week 12) | 12 hours (n=228 QVA149; 236 flut/salm) | 3.45 liters | Standard Error 0.05 |
| 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 |
| Fluticasone/Salmeterol | Forced Vital Capacity at All-time Points (Week 12) | 12 hours (n=228 QVA149; 236 flut/salm) | 3.26 liters | Standard Error 0.049 |
| Fluticasone/Salmeterol | Forced Vital Capacity at All-time Points (Week 12) | -45 minutes (n=230 QVA149; 237 flut/salm) | 3.16 liters | Standard Error 0.044 |
| Fluticasone/Salmeterol | Forced Vital Capacity at All-time Points (Week 12) | -15 minutes (n=228 QVA149; 235 flut/salm) | 3.17 liters | Standard Error 0.045 |
| Fluticasone/Salmeterol | Forced Vital Capacity at All-time Points (Week 12) | 5 minutes (n=229 QVA149; 236 flut/salm) | 3.20 liters | Standard Error 0.046 |
| Fluticasone/Salmeterol | Forced Vital Capacity at All-time Points (Week 12) | 30 minutes (n=229 QVA149; 235 flut/salm) | 3.23 liters | Standard Error 0.046 |
| Fluticasone/Salmeterol | Forced Vital Capacity at All-time Points (Week 12) | 1 hour (n=228 QVA149; 236 flut/salm) | 3.26 liters | Standard Error 0.047 |
| Fluticasone/Salmeterol | Forced Vital Capacity at All-time Points (Week 12) | 2 hours (n=229 QVA149; 237 flut/salm) | 3.31 liters | Standard Error 0.046 |
| Fluticasone/Salmeterol | Forced Vital Capacity at All-time Points (Week 12) | 4 hours (n=228 QVA149; 237 flut/salm) | 3.33 liters | Standard Error 0.048 |
| Fluticasone/Salmeterol | Forced Vital Capacity at All-time Points (Week 12) | 8 hours (n=228 QVA149; 237 flut/salm) | 3.27 liters | Standard Error 0.046 |
Secondary
Forced Vital Capacity at All-time Points (Week 26)
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.
Time frame: -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.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| QVA149 | Forced Vital Capacity at All-time Points (Week 26) | -15 minutes (n=213 QVA149; 215 flut/salm) | 3.33 liters | Standard Error 0.044 |
| QVA149 | Forced Vital Capacity at All-time Points (Week 26) | 2 hours (n=212 QVA149; 216 flut/salm) | 3.51 liters | Standard Error 0.051 |
| QVA149 | Forced Vital Capacity at All-time Points (Week 26) | 30 minutes (n=212 QVA149; 214 flut/salm) | 3.47 liters | Standard Error 0.053 |
| QVA149 | Forced Vital Capacity at All-time Points (Week 26) | 4 hours (n=212 QVA149; 215 flut/salm) | 3.45 liters | Standard Error 0.053 |
| QVA149 | Forced Vital Capacity at All-time Points (Week 26) | 5 minutes (n=212 QVA149; 215 flut/salm) | 3.42 liters | Standard Error 0.051 |
| QVA149 | Forced Vital Capacity at All-time Points (Week 26) | 8 hours (n=212 QVA149; 216 flut/salm) | 3.40 liters | Standard Error 0.053 |
| QVA149 | Forced Vital Capacity at All-time Points (Week 26) | 1 hour (n=212 QVA149; 216 flut/salm) | 3.50 liters | Standard Error 0.051 |
| QVA149 | Forced Vital Capacity at All-time Points (Week 26) | 12 hours (n=211 QVA149; 213 flut/salm) | 3.40 liters | Standard Error 0.053 |
| 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 |
| Fluticasone/Salmeterol | Forced Vital Capacity at All-time Points (Week 26) | 12 hours (n=211 QVA149; 213 flut/salm) | 3.18 liters | Standard Error 0.051 |
| Fluticasone/Salmeterol | Forced Vital Capacity at All-time Points (Week 26) | -45 minutes (n=213 QVA149; 216 flut/salm) | 3.13 liters | Standard Error 0.045 |
| Fluticasone/Salmeterol | Forced Vital Capacity at All-time Points (Week 26) | -15 minutes (n=213 QVA149; 215 flut/salm) | 3.12 liters | Standard Error 0.043 |
| Fluticasone/Salmeterol | Forced Vital Capacity at All-time Points (Week 26) | 5 minutes (n=212 QVA149; 215 flut/salm) | 3.17 liters | Standard Error 0.049 |
| Fluticasone/Salmeterol | Forced Vital Capacity at All-time Points (Week 26) | 30 minutes (n=212 QVA149; 214 flut/salm) | 3.23 liters | Standard Error 0.051 |
| Fluticasone/Salmeterol | Forced Vital Capacity at All-time Points (Week 26) | 1 hour (n=212 QVA149; 216 flut/salm) | 3.23 liters | Standard Error 0.049 |
| Fluticasone/Salmeterol | Forced Vital Capacity at All-time Points (Week 26) | 2 hours (n=212 QVA149; 216 flut/salm) | 3.29 liters | Standard Error 0.049 |
| Fluticasone/Salmeterol | Forced Vital Capacity at All-time Points (Week 26) | 4 hours (n=212 QVA149; 215 flut/salm) | 3.28 liters | Standard Error 0.05 |
| Fluticasone/Salmeterol | Forced Vital Capacity at All-time Points (Week 26) | 8 hours (n=212 QVA149; 216 flut/salm) | 3.21 liters | Standard Error 0.05 |
Secondary
Inspiratory Capacity (IC) at All-time Points (12 Weeks)
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.
Time frame: 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.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| 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 |
| QVA149 | Inspiratory Capacity (IC) at All-time Points (12 Weeks) | 25 minutes (n=56 QVA149; 71 flut/salm) | 2.55 Liters | Standard Error 0.075 |
| QVA149 | Inspiratory Capacity (IC) at All-time Points (12 Weeks) | 1 hour (n=59 QVA149; 68 flut/salm) | 2.54 Liters | Standard Error 0.079 |
| QVA149 | Inspiratory Capacity (IC) at All-time Points (12 Weeks) | 3 hours (n=54 QVA149; 67 flut/salm) | 2.52 Liters | Standard Error 0.086 |
| QVA149 | Inspiratory Capacity (IC) at All-time Points (12 Weeks) | 7 hours (n=58 QVA149; 67 flut/salm) | 2.42 Liters | Standard Error 0.08 |
| QVA149 | Inspiratory Capacity (IC) at All-time Points (12 Weeks) | 11 hours (n=49 QVA149; 72 flut/salm) | 2.40 Liters | Standard Error 0.079 |
| Fluticasone/Salmeterol | Inspiratory Capacity (IC) at All-time Points (12 Weeks) | 7 hours (n=58 QVA149; 67 flut/salm) | 2.41 Liters | Standard Error 0.073 |
| Fluticasone/Salmeterol | Inspiratory Capacity (IC) at All-time Points (12 Weeks) | -20 minutes (n=51 QVA149; 65 flut/salm) | 2.31 Liters | Standard Error 0.073 |
| Fluticasone/Salmeterol | Inspiratory Capacity (IC) at All-time Points (12 Weeks) | 3 hours (n=54 QVA149; 67 flut/salm) | 2.45 Liters | Standard Error 0.079 |
| Fluticasone/Salmeterol | Inspiratory Capacity (IC) at All-time Points (12 Weeks) | 25 minutes (n=56 QVA149; 71 flut/salm) | 2.42 Liters | Standard Error 0.068 |
| Fluticasone/Salmeterol | Inspiratory Capacity (IC) at All-time Points (12 Weeks) | 11 hours (n=49 QVA149; 72 flut/salm) | 2.34 Liters | Standard Error 0.07 |
| Fluticasone/Salmeterol | Inspiratory Capacity (IC) at All-time Points (12 Weeks) | 1 hour (n=59 QVA149; 68 flut/salm) | 2.43 Liters | Standard Error 0.072 |
Secondary
Inspiratory Capacity (IC) at All-time Points (26 Weeks)
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.
Time frame: 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.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| 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 |
| QVA149 | Inspiratory Capacity (IC) at All-time Points (26 Weeks) | 25 minutes (n=58 QVA149; 63 flut/salm) | 2.41 Liters | Standard Error 0.088 |
| QVA149 | Inspiratory Capacity (IC) at All-time Points (26 Weeks) | 1 hour (n=53 QVA149; 63 flut/salm) | 2.38 Liters | Standard Error 0.087 |
| QVA149 | Inspiratory Capacity (IC) at All-time Points (26 Weeks) | 3 hours (n=52 QVA149; 60 flut/salm) | 2.33 Liters | Standard Error 0.09 |
| QVA149 | Inspiratory Capacity (IC) at All-time Points (26 Weeks) | 7 hours (n=56 QVA149; 61 flut/salm) | 2.40 Liters | Standard Error 0.82 |
| QVA149 | Inspiratory Capacity (IC) at All-time Points (26 Weeks) | 11 hours (n=57 QVA149; 66 flut/salm) | 2.37 Liters | Standard Error 0.084 |
| Fluticasone/Salmeterol | Inspiratory Capacity (IC) at All-time Points (26 Weeks) | 7 hours (n=56 QVA149; 61 flut/salm) | 2.30 Liters | Standard Error 0.075 |
| Fluticasone/Salmeterol | Inspiratory Capacity (IC) at All-time Points (26 Weeks) | -20 minutes (n=53 QVA149; 63 flut/salm) | 2.22 Liters | Standard Error 0.071 |
| Fluticasone/Salmeterol | Inspiratory Capacity (IC) at All-time Points (26 Weeks) | 3 hours (n=52 QVA149; 60 flut/salm) | 2.32 Liters | Standard Error 0.08 |
| Fluticasone/Salmeterol | Inspiratory Capacity (IC) at All-time Points (26 Weeks) | 25 minutes (n=58 QVA149; 63 flut/salm) | 2.34 Liters | Standard Error 0.08 |
| Fluticasone/Salmeterol | Inspiratory Capacity (IC) at All-time Points (26 Weeks) | 11 hours (n=57 QVA149; 66 flut/salm) | 2.27 Liters | Standard Error 0.075 |
| Fluticasone/Salmeterol | Inspiratory Capacity (IC) at All-time Points (26 Weeks) | 1 hour (n=53 QVA149; 63 flut/salm) | 2.35 Liters | Standard Error 0.079 |
Secondary
Mean Change From Baseline in Daily Number of Puffs of Rescue Medication
Participants maintained a diary to record the daily number of puffs of rescue medication used to treat COPD symptoms.
Time frame: 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.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| QVA149 | Mean Change From Baseline in Daily Number of Puffs of Rescue Medication | Weeks 1 to12 | -2.18 puffs | Standard Error 0.187 |
| QVA149 | Mean Change From Baseline in Daily Number of Puffs of Rescue Medication | Weeks 1 to 26 | -2.32 puffs | Standard Error 0.194 |
| Fluticasone/Salmeterol | Mean Change From Baseline in Daily Number of Puffs of Rescue Medication | Weeks 1 to12 | -1.90 puffs | Standard Error 0.184 |
| Fluticasone/Salmeterol | Mean Change From Baseline in Daily Number of Puffs of Rescue Medication | Weeks 1 to 26 | -1.93 puffs | Standard Error 0.191 |
Secondary
Number of Participants With Adverse Events
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.
Time frame: 26 weeks
Population: Safety set includes all participants who received at least one dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| QVA149 | Number of Participants With Adverse Events | Discontinued due to non-Serious Adverse Events | 17 participants |
| QVA149 | Number of Participants With Adverse Events | Any Adverse Event | 143 participants |
| QVA149 | Number of Participants With Adverse Events | Death | 0 participants |
| QVA149 | Number of Participants With Adverse Events | Serious Adverse Events | 13 participants |
| QVA149 | Number of Participants With Adverse Events | Discontinued due to Adverse Events | 22 participants |
| QVA149 | Number of Participants With Adverse Events | Discontinued due to Serious Adverse Events | 5 participants |
| Fluticasone/Salmeterol | Number of Participants With Adverse Events | Discontinued due to Adverse Events | 27 participants |
| Fluticasone/Salmeterol | Number of Participants With Adverse Events | Discontinued due to non-Serious Adverse Events | 18 participants |
| Fluticasone/Salmeterol | Number of Participants With Adverse Events | Serious Adverse Events | 14 participants |
| Fluticasone/Salmeterol | Number of Participants With Adverse Events | Any Adverse Event | 159 participants |
| Fluticasone/Salmeterol | Number of Participants With Adverse Events | Discontinued due to Serious Adverse Events | 9 participants |
| Fluticasone/Salmeterol | Number of Participants With Adverse Events | Death | 1 participants |
Secondary
Standardized Forced Expiratory Volume in 1 Second Area Under the Curve (FEV1 AUC) 0-12 Hours
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.
Time frame: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| QVA149 | Standardized Forced Expiratory Volume in 1 Second Area Under the Curve (FEV1 AUC) 0-12 Hours | 1.71 liters | Standard Error 0.023 |
| Fluticasone/Salmeterol | Standardized Forced Expiratory Volume in 1 Second Area Under the Curve (FEV1 AUC) 0-12 Hours | 1.59 liters | Standard Error 0.022 |
Secondary
Total Score of the St. George's Respiratory Questionnaire (SGRQ-C)
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.
Time frame: 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.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| 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 |
| QVA149 | 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 |
| Fluticasone/Salmeterol | Total Score of the St. George's Respiratory Questionnaire (SGRQ-C) | 12 weeks (n=230 QVA149; 238 flut/salm) | 36.03 units on a scale | Standard Error 1.132 |
| Fluticasone/Salmeterol | Total Score of the St. George's Respiratory Questionnaire (SGRQ-C) | 26 weeks (n=211 QVA149; 216 flut/salm) | 36.68 units on a scale | Standard Error 1.386 |