Chronic Obstructive Pulmonary Disease
Conditions
Keywords
chronic obstructive pulmonary disease
Brief summary
To demonstrate the non-inferiority of QVA149 110/50 µg o.d. to fluticasone/salmeterol 500/50 µg b.i.d. in terms of trough Forced Expiratory Volume in one second (FEV1) (mean of 23 hours 15 min and 23 hours 45 min post QVA149 dose) following 26 weeks of treatment in patients with moderate to severe COPD
Detailed description
To demonstrate the non-inferiority of QVA149 110/50 µg o.d. to fluticasone/salmeterol 500/50 µg b.i.d. in terms of trough Forced Expiratory Volume in one second (FEV1) (mean of 23 hours 15 min and 23 hours 45 min post QVA149 dose) following 26 weeks of treatment in patients with moderate to severe COPD. The study population will consist of approximate 736 male and female adults (age 40 years and greater) with a clinical diagnosis of stable COPD \[GOLD (2010)\] and a smoking history of at least 10 pack years. It is anticipated that approximately 981 patients will need to be screened in order to randomize 736 patients into 2 treatment arms of the study with an equal randomization ratio, meaning QVA149 (368 patients), fluticasone/salmeterol (368 patients). Treatment randomization will be stratified by current/ex-smoker status and prior ICS use. It is intended that 552 patients will complete the study at Week 26 without major protocol deviations. Dropouts will not be replaced. This will be a multi-national study, including China, and at least two other countries. Standardization FEV1 AUC0-12h will be performed in a subgroup of around 100 patients (50 patients per treatment arm) in pre-selected centers.
Interventions
DRUGQVA149
QVA149 110/50 µg capsules q.d. for inhalation, delivered via Novartis single dose dry powder inhaler (SDDPI).
Active fluticasone/salmeterol (500/50µg) b.i.d via a dry power inhaler Accuhaler® device.
Placebo to QVA149 with SDDPI
Placebo to fluticasone/salmeterol with Accuhaler
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
* Patients with moderate to severe stable COPD (Stage II or Stage III) according to Global Initiative for Chronic Obstructive Lung Disease (GOLD) Guideline. Current or ex-smokers who have a 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/FVC \< 0.7. Modified Medical Research Council (mMRC) grade of at least 2 at Visit 2.
Exclusion criteria
* Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive Human Chorionic Gonadotropin (hCG) laboratory test. Patents with narrow-angle glaucoma, symptomatic benign prostatic hyperplasia (BPH), bladder-neck obstruction, moderate to severe renal impairment or urinary retention. BPH patients who are stable on treatment can be considered. Patients with a history of long QT syndrome or whose QTc measured at run-in (Visit 2) (Fridericia method) is prolonged (\>450 ms for males and females) as confirmed by the central Electrocardiogram (ECG) assessor. Patients with Type I or uncontrolled Type II diabetes. Patients who have not achieved spirometry result at Visit 2 in accordance with American Thoracic Society/European Respiratory Society (ATS/ERS) criteria for acceptability and repeatability. Patients with, a) any history of asthma or, b) onset of respiratory symptoms prior to age 40 years. Patients with concomitant pulmonary disease (e.g. lung fibrosis, primary bronchiectasis, sarcoidosis, interstitial lung disorder, pulmonary hypertension). Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Trough Forced Expiratory Volume in One Second (FEV1) Following 26 Weeks of Treatment to Demonstrate the Non-inferiority of QVA149 110/50 μg o.d. to Fluticasone/Salmeterol 500/50 μg b.i.d | 26 weeks | Measurement of QVA149 110/50 μg o.d. to fluticasone/salmeterol 500/50 μg b.i.d. in terms of trough FEV1 (mean of 23 h 15 min and 23 h 45 min post QVA149 dose) following 26 weeks of treatment in patients with moderate to severe COPD. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Standardized Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC) 0-4 Hours | Day 1, 12 and 26 weeks | Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC) 0-4h at Day 1 was measured via spirometry conducted according to internationally accepted standards. Measurements were made at 0, 5, 15, and 30 minutes; and 1, 2, 3 and 4 hours post-dose. The standardized AUC FEV1 was calculated as the sum of trapezoids divided by the length of time. Mixed model used: AUC FEV1 = treatment + baseline FEV1 + FEV1 reversibility components + baseline smoking status + baseline ICS use + country + center (country) + error. Center was included as a random effect nested within country. |
| Analysis of FEV1 (L) Trough Response (Pre-dose) Over the Whole Treatment Period | 6,12,18 and 26 weeks | Average of Trough Forced Expiratory Volume in one second (FEV1) |
| Analysis of Trough FVC (L) Over the Whole Treatment Period | 12 and 26 weeks | Average of Trough Forced Vital Capacity (FVC) at 23 hours 15 min and the 23 hours 45 min post dose |
| Trough Forced Expiratory Volume in One Second (FEV1) Following 26 Weeks of Treatment to Demonstrate the Superiority of QVA 110/50μg o.d. to Fluticasone/Salmeterol 500/50 μg b.i.d | 26 weeks | — |
| Analysis of the TDI Focal Score Over the Whole Treatment Period | 12 and 26 weeks | The Transition Dyspnea Index (TDI) total score after 12 and 26 weeks of treatment will be analyzed using the same mixed model as specified for the primary analysis with the Baseline Dyspnea Index (BDI) total score as the baseline.Total score ranging - 9 to + 9. The lower the score, the more deterioration in severity of dyspnea. One additional option in each category, which does not contribute to the score, allows for circumstances in which impairment is due to reasons other than dyspnea. .Baseline 12 weeks and Baseline 26 weeks, were the baseline scores for available participants analyzed for each time point. |
| Rescue Medication Use: Summary of the Mean Daily, Daytime and Nighttime Number of Puffs of Rescue Medication, by 4 Weekly Intervals | 12 and 26 weeks | The number of puffs of rescue medication taken in the previous 12 hours will be recorded in the Patient Diary in the morning and evening. Baseline 12 weeks and Baseline 26 weeks, were the baseline scores for available participants analyzed for each time point. Less puffs taken is better. |
| Symptoms Reported Using E-diary Over 12 and 26 Weeks of Treatment | 26 weeks | Percentage of nights with 'no nighttime awakenings', percentage of days with 'no daytime symptoms', and percentage of 'days able to perform usual daily activities' over 26 weeks (FAS) |
| Health Related Quality of Life Analysis of SGRQ Total Score After 26 Weeks of Treatment | 26 weeks | A Total and three component scores are calculated: Symptoms; Activity; Impacts. Each component of the questionnaire is scored separately:The score for each component is calculated separately by dividing the summed weights by the maximum possible weight for that component and expressing the result as a percentage: Score = 100 x Summed weights from all positive items in that component divided by Sum of weights for all items in that component The Total score is calculated in similar way: Score = 100 x Summed weights from all positive items in the questionnaire divided by Sum of weights for all items in the questionnaire Sum of maximum possible weights for each component and Total: Symptoms 566.2 Activity 982.9 Impacts 1652.8 Total (sum of maximum for all three components) 3201.9 The proportion of patients who achieve a clinically important improvement of at least 4 units in the total SGRQ will be analyzed. The higher the score the more symptoms of disease are present. |
Countries
Argentina, Chile, China, Taiwan
Participant flow
Recruitment details
Patients were randomized into 2 treatment arms of the study with an equal 1:1 randomization ratio: QVA149 and Flut/Salm
Pre-assignment details
A total of 1189 patients were screened; 744 (62.6%) completed the screening phase while 445 (37.4%) patients discontinued prior to completion of the screening phase
Participants by arm
| Arm | Count |
|---|---|
| QVA149 QVA149 110/50 µg o.d., delivered via a single-dose dry powder inhaler (SDDPI), consisting of a fixed dose combination of indacaterol 110µg and NVA237 50µg | 372 |
| Fluticasone/Salmeterol Fluticasone/salmeterol 500/50 µg b.i.d., delivered via a dry powder inhaler Accuhaler® device | 369 |
| Total | 741 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Abnormal test procedure results | 1 | 0 |
| Overall Study | administrative problems | 2 | 6 |
| Overall Study | Adverse Event | 11 | 18 |
| Overall Study | Death | 2 | 0 |
| Overall Study | In ability to use device | 1 | 1 |
| Overall Study | Lack of Efficacy | 3 | 3 |
| Overall Study | Lost to Follow-up | 0 | 2 |
| Overall Study | no longer needed study drug | 0 | 1 |
| Overall Study | Protocol Violation | 3 | 2 |
| Overall Study | Withdrawal by Subject | 6 | 6 |
Baseline characteristics
| Characteristic | Fluticasone/Salmeterol | Total | QVA149 |
|---|---|---|---|
| Age, Continuous | 65.3 years STANDARD_DEVIATION 7.91 | 65.0 years STANDARD_DEVIATION 7.87 | 64.8 years STANDARD_DEVIATION 7.82 |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 309 Participants | 623 Participants | 314 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) White | 58 Participants | 113 Participants | 55 Participants |
| Sex: Female, Male Female | 38 Participants | 69 Participants | 31 Participants |
| Sex: Female, Male Male | 331 Participants | 672 Participants | 341 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 107 / 372 | 135 / 369 |
| serious Total, serious adverse events | 20 / 372 | 35 / 369 |
Outcome results
Primary
Trough Forced Expiratory Volume in One Second (FEV1) Following 26 Weeks of Treatment to Demonstrate the Non-inferiority of QVA149 110/50 μg o.d. to Fluticasone/Salmeterol 500/50 μg b.i.d
Measurement of QVA149 110/50 μg o.d. to fluticasone/salmeterol 500/50 μg b.i.d. in terms of trough FEV1 (mean of 23 h 15 min and 23 h 45 min post QVA149 dose) following 26 weeks of treatment in patients with moderate to severe COPD.
Time frame: 26 weeks
Population: FAS
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| QVA149 | Trough Forced Expiratory Volume in One Second (FEV1) Following 26 Weeks of Treatment to Demonstrate the Non-inferiority of QVA149 110/50 μg o.d. to Fluticasone/Salmeterol 500/50 μg b.i.d | 1.248 liters | Standard Error 0.0173 |
| Fluticasone/Salmeterol | Trough Forced Expiratory Volume in One Second (FEV1) Following 26 Weeks of Treatment to Demonstrate the Non-inferiority of QVA149 110/50 μg o.d. to Fluticasone/Salmeterol 500/50 μg b.i.d | 1.176 liters | Standard Error 0.0172 |
Secondary
Analysis of FEV1 (L) Trough Response (Pre-dose) Over the Whole Treatment Period
Average of Trough Forced Expiratory Volume in one second (FEV1)
Time frame: 6,12,18 and 26 weeks
Population: Full analysis set
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| QVA149 | Analysis of FEV1 (L) Trough Response (Pre-dose) Over the Whole Treatment Period | Week 6 (n=356,341) | 1.256 liter | Standard Error 0.0151 |
| QVA149 | Analysis of FEV1 (L) Trough Response (Pre-dose) Over the Whole Treatment Period | week 12 (n=346,333) | 1.265 liter | Standard Error 0.0158 |
| QVA149 | Analysis of FEV1 (L) Trough Response (Pre-dose) Over the Whole Treatment Period | week 18 (n=339,332) | 1.252 liter | Standard Error 0.0166 |
| QVA149 | Analysis of FEV1 (L) Trough Response (Pre-dose) Over the Whole Treatment Period | week 26 (n=338,324) | 1.226 liter | Standard Error 0.0171 |
| Fluticasone/Salmeterol | Analysis of FEV1 (L) Trough Response (Pre-dose) Over the Whole Treatment Period | week 26 (n=338,324) | 1.142 liter | Standard Error 0.0171 |
| Fluticasone/Salmeterol | Analysis of FEV1 (L) Trough Response (Pre-dose) Over the Whole Treatment Period | Week 6 (n=356,341) | 1.184 liter | Standard Error 0.0149 |
| Fluticasone/Salmeterol | Analysis of FEV1 (L) Trough Response (Pre-dose) Over the Whole Treatment Period | week 18 (n=339,332) | 1.174 liter | Standard Error 0.0164 |
| Fluticasone/Salmeterol | Analysis of FEV1 (L) Trough Response (Pre-dose) Over the Whole Treatment Period | week 12 (n=346,333) | 1.191 liter | Standard Error 0.0156 |
Secondary
Analysis of the TDI Focal Score Over the Whole Treatment Period
The Transition Dyspnea Index (TDI) total score after 12 and 26 weeks of treatment will be analyzed using the same mixed model as specified for the primary analysis with the Baseline Dyspnea Index (BDI) total score as the baseline.Total score ranging - 9 to + 9. The lower the score, the more deterioration in severity of dyspnea. One additional option in each category, which does not contribute to the score, allows for circumstances in which impairment is due to reasons other than dyspnea. .Baseline 12 weeks and Baseline 26 weeks, were the baseline scores for available participants analyzed for each time point.
Time frame: 12 and 26 weeks
Population: Full Analysis Set
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| QVA149 | Analysis of the TDI Focal Score Over the Whole Treatment Period | Baseline 12 weeks (n=348,337) | 6.36 Numbers on a scale | Standard Error 0.096 |
| QVA149 | Analysis of the TDI Focal Score Over the Whole Treatment Period | 12 weeks (n=348,337) | 2.62 Numbers on a scale | Standard Error 0.24 |
| QVA149 | Analysis of the TDI Focal Score Over the Whole Treatment Period | Baseline 26 weeks (n=335,326) | 6.38 Numbers on a scale | Standard Error 0.097 |
| QVA149 | Analysis of the TDI Focal Score Over the Whole Treatment Period | 26 weeks (n=335,326) | 3.02 Numbers on a scale | Standard Error 0.266 |
| Fluticasone/Salmeterol | Analysis of the TDI Focal Score Over the Whole Treatment Period | 26 weeks (n=335,326) | 2.86 Numbers on a scale | Standard Error 0.266 |
| Fluticasone/Salmeterol | Analysis of the TDI Focal Score Over the Whole Treatment Period | Baseline 12 weeks (n=348,337) | 6.36 Numbers on a scale | Standard Error 0.104 |
| Fluticasone/Salmeterol | Analysis of the TDI Focal Score Over the Whole Treatment Period | Baseline 26 weeks (n=335,326) | 6.40 Numbers on a scale | Standard Error 0.105 |
| Fluticasone/Salmeterol | Analysis of the TDI Focal Score Over the Whole Treatment Period | 12 weeks (n=348,337) | 2.40 Numbers on a scale | Standard Error 0.238 |
Secondary
Analysis of Trough FVC (L) Over the Whole Treatment Period
Average of Trough Forced Vital Capacity (FVC) at 23 hours 15 min and the 23 hours 45 min post dose
Time frame: 12 and 26 weeks
Population: Full Analysis Set
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| QVA149 | Analysis of Trough FVC (L) Over the Whole Treatment Period | Day 1 (n=350,351) | 3.040 liter | Standard Error 0.0288 |
| QVA149 | Analysis of Trough FVC (L) Over the Whole Treatment Period | Week 12 (n=342,332) | 3.036 liter | Standard Error 0.0304 |
| QVA149 | Analysis of Trough FVC (L) Over the Whole Treatment Period | week 26 (n= 333,323) | 2.966 liter | Standard Error 0.0334 |
| Fluticasone/Salmeterol | Analysis of Trough FVC (L) Over the Whole Treatment Period | Day 1 (n=350,351) | 2.957 liter | Standard Error 0.028 |
| Fluticasone/Salmeterol | Analysis of Trough FVC (L) Over the Whole Treatment Period | Week 12 (n=342,332) | 2.835 liter | Standard Error 0.0302 |
| Fluticasone/Salmeterol | Analysis of Trough FVC (L) Over the Whole Treatment Period | week 26 (n= 333,323) | 2.793 liter | Standard Error 0.0333 |
Secondary
Health Related Quality of Life Analysis of SGRQ Total Score After 26 Weeks of Treatment
A Total and three component scores are calculated: Symptoms; Activity; Impacts. Each component of the questionnaire is scored separately:The score for each component is calculated separately by dividing the summed weights by the maximum possible weight for that component and expressing the result as a percentage: Score = 100 x Summed weights from all positive items in that component divided by Sum of weights for all items in that component The Total score is calculated in similar way: Score = 100 x Summed weights from all positive items in the questionnaire divided by Sum of weights for all items in the questionnaire Sum of maximum possible weights for each component and Total: Symptoms 566.2 Activity 982.9 Impacts 1652.8 Total (sum of maximum for all three components) 3201.9 The proportion of patients who achieve a clinically important improvement of at least 4 units in the total SGRQ will be analyzed. The higher the score the more symptoms of disease are present.
Time frame: 26 weeks
Population: Full Analysis set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| QVA149 | Health Related Quality of Life Analysis of SGRQ Total Score After 26 Weeks of Treatment | Week 26 (n= 340,329) | 31.20 numbers on a scale | Standard Error 1.118 |
| QVA149 | Health Related Quality of Life Analysis of SGRQ Total Score After 26 Weeks of Treatment | Week 26 LOCF(n=354,342) | 31.74 numbers on a scale | Standard Error 1.136 |
| Fluticasone/Salmeterol | Health Related Quality of Life Analysis of SGRQ Total Score After 26 Weeks of Treatment | Week 26 (n= 340,329) | 32.00 numbers on a scale | Standard Error 1.118 |
| Fluticasone/Salmeterol | Health Related Quality of Life Analysis of SGRQ Total Score After 26 Weeks of Treatment | Week 26 LOCF(n=354,342) | 32.43 numbers on a scale | Standard Error 1.13 |
Secondary
Rescue Medication Use: Summary of the Mean Daily, Daytime and Nighttime Number of Puffs of Rescue Medication, by 4 Weekly Intervals
The number of puffs of rescue medication taken in the previous 12 hours will be recorded in the Patient Diary in the morning and evening. Baseline 12 weeks and Baseline 26 weeks, were the baseline scores for available participants analyzed for each time point. Less puffs taken is better.
Time frame: 12 and 26 weeks
Population: Full Analysis set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| QVA149 | Rescue Medication Use: Summary of the Mean Daily, Daytime and Nighttime Number of Puffs of Rescue Medication, by 4 Weekly Intervals | Baseline Daytime 12-16 weeks (n=329,318) | 1.57 # of puffs | Standard Deviation 1.934 |
| QVA149 | Rescue Medication Use: Summary of the Mean Daily, Daytime and Nighttime Number of Puffs of Rescue Medication, by 4 Weekly Intervals | Daytime 12-16 weeks (n=329,318) | 0.66 # of puffs | Standard Deviation 1.185 |
| QVA149 | Rescue Medication Use: Summary of the Mean Daily, Daytime and Nighttime Number of Puffs of Rescue Medication, by 4 Weekly Intervals | Baseline Nighttime 12-16 weeks (n=322,307) | 1.25 # of puffs | Standard Deviation 1.5954 |
| QVA149 | Rescue Medication Use: Summary of the Mean Daily, Daytime and Nighttime Number of Puffs of Rescue Medication, by 4 Weekly Intervals | Nighttime 12-16 weeks (n=322,307) | 0.52 # of puffs | Standard Deviation 1.007 |
| QVA149 | Rescue Medication Use: Summary of the Mean Daily, Daytime and Nighttime Number of Puffs of Rescue Medication, by 4 Weekly Intervals | Baseline Daytime 24-26 weeks (n=326,315) | 1.54 # of puffs | Standard Deviation 1.885 |
| QVA149 | Rescue Medication Use: Summary of the Mean Daily, Daytime and Nighttime Number of Puffs of Rescue Medication, by 4 Weekly Intervals | Daytime 24-26 weeks (n=326,315) | 0.63 # of puffs | Standard Deviation 1.226 |
| QVA149 | Rescue Medication Use: Summary of the Mean Daily, Daytime and Nighttime Number of Puffs of Rescue Medication, by 4 Weekly Intervals | Baseline Night time 24-26 weeks (n=320,304) | 1.23 # of puffs | Standard Deviation 1.588 |
| QVA149 | Rescue Medication Use: Summary of the Mean Daily, Daytime and Nighttime Number of Puffs of Rescue Medication, by 4 Weekly Intervals | Night time 24-26 weeks (n=320,304) | 0.52 # of puffs | Standard Deviation 1.087 |
| Fluticasone/Salmeterol | Rescue Medication Use: Summary of the Mean Daily, Daytime and Nighttime Number of Puffs of Rescue Medication, by 4 Weekly Intervals | Night time 24-26 weeks (n=320,304) | 0.48 # of puffs | Standard Deviation 0.923 |
| Fluticasone/Salmeterol | Rescue Medication Use: Summary of the Mean Daily, Daytime and Nighttime Number of Puffs of Rescue Medication, by 4 Weekly Intervals | Baseline Daytime 12-16 weeks (n=329,318) | 1.69 # of puffs | Standard Deviation 2.13 |
| Fluticasone/Salmeterol | Rescue Medication Use: Summary of the Mean Daily, Daytime and Nighttime Number of Puffs of Rescue Medication, by 4 Weekly Intervals | Baseline Daytime 24-26 weeks (n=326,315) | 1.70 # of puffs | Standard Deviation 2.16 |
| Fluticasone/Salmeterol | Rescue Medication Use: Summary of the Mean Daily, Daytime and Nighttime Number of Puffs of Rescue Medication, by 4 Weekly Intervals | Daytime 12-16 weeks (n=329,318) | 0.61 # of puffs | Standard Deviation 1.117 |
| Fluticasone/Salmeterol | Rescue Medication Use: Summary of the Mean Daily, Daytime and Nighttime Number of Puffs of Rescue Medication, by 4 Weekly Intervals | Baseline Night time 24-26 weeks (n=320,304) | 1.21 # of puffs | Standard Deviation 1.702 |
| Fluticasone/Salmeterol | Rescue Medication Use: Summary of the Mean Daily, Daytime and Nighttime Number of Puffs of Rescue Medication, by 4 Weekly Intervals | Baseline Nighttime 12-16 weeks (n=322,307) | 1.24 # of puffs | Standard Deviation 1.707 |
| Fluticasone/Salmeterol | Rescue Medication Use: Summary of the Mean Daily, Daytime and Nighttime Number of Puffs of Rescue Medication, by 4 Weekly Intervals | Daytime 24-26 weeks (n=326,315) | 0.62 # of puffs | Standard Deviation 1.135 |
| Fluticasone/Salmeterol | Rescue Medication Use: Summary of the Mean Daily, Daytime and Nighttime Number of Puffs of Rescue Medication, by 4 Weekly Intervals | Nighttime 12-16 weeks (n=322,307) | 0.49 # of puffs | Standard Deviation 0.96 |
Secondary
Standardized Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC) 0-4 Hours
Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC) 0-4h at Day 1 was measured via spirometry conducted according to internationally accepted standards. Measurements were made at 0, 5, 15, and 30 minutes; and 1, 2, 3 and 4 hours post-dose. The standardized AUC FEV1 was calculated as the sum of trapezoids divided by the length of time. Mixed model used: AUC FEV1 = treatment + baseline FEV1 + FEV1 reversibility components + baseline smoking status + baseline ICS use + country + center (country) + error. Center was included as a random effect nested within country.
Time frame: Day 1, 12 and 26 weeks
Population: Full Analysis set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| QVA149 | Standardized Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC) 0-4 Hours | Day 1 (n=369,364) | 1.317 Liter | Standard Deviation 0.0096 |
| QVA149 | Standardized Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC) 0-4 Hours | 12 weeks (n=350,338) | 1.388 Liter | Standard Deviation 0.0163 |
| QVA149 | Standardized Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC) 0-4 Hours | 26 weeks (n=339,323) | 1.351 Liter | Standard Deviation 0.0167 |
| Fluticasone/Salmeterol | Standardized Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC) 0-4 Hours | Day 1 (n=369,364) | 1.252 Liter | Standard Deviation 0.0094 |
| Fluticasone/Salmeterol | Standardized Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC) 0-4 Hours | 12 weeks (n=350,338) | 1.262 Liter | Standard Deviation 0.0161 |
| Fluticasone/Salmeterol | Standardized Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC) 0-4 Hours | 26 weeks (n=339,323) | 1.229 Liter | Standard Deviation 0.0167 |
Secondary
Symptoms Reported Using E-diary Over 12 and 26 Weeks of Treatment
Percentage of nights with 'no nighttime awakenings', percentage of days with 'no daytime symptoms', and percentage of 'days able to perform usual daily activities' over 26 weeks (FAS)
Time frame: 26 weeks
Population: Full Analysis Set
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| QVA149 | Symptoms Reported Using E-diary Over 12 and 26 Weeks of Treatment | % nights 'no nighttime awakenings' (n=336,322) | 67.57 % days in study | Standard Error 2.138 |
| QVA149 | Symptoms Reported Using E-diary Over 12 and 26 Weeks of Treatment | % days with 'no daytime symptoms' (n=341,334) | 7.31 % days in study | Standard Error 1.466 |
| QVA149 | Symptoms Reported Using E-diary Over 12 and 26 Weeks of Treatment | % days able perform daily activities (n=341,334) | 44.02 % days in study | Standard Error 2.2 |
| Fluticasone/Salmeterol | Symptoms Reported Using E-diary Over 12 and 26 Weeks of Treatment | % nights 'no nighttime awakenings' (n=336,322) | 67.86 % days in study | Standard Error 2.101 |
| Fluticasone/Salmeterol | Symptoms Reported Using E-diary Over 12 and 26 Weeks of Treatment | % days with 'no daytime symptoms' (n=341,334) | 10.22 % days in study | Standard Error 1.425 |
| Fluticasone/Salmeterol | Symptoms Reported Using E-diary Over 12 and 26 Weeks of Treatment | % days able perform daily activities (n=341,334) | 42.16 % days in study | Standard Error 2.14 |
Secondary
Trough Forced Expiratory Volume in One Second (FEV1) Following 26 Weeks of Treatment to Demonstrate the Superiority of QVA 110/50μg o.d. to Fluticasone/Salmeterol 500/50 μg b.i.d
Time frame: 26 weeks
Population: FAS
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| QVA149 | Trough Forced Expiratory Volume in One Second (FEV1) Following 26 Weeks of Treatment to Demonstrate the Superiority of QVA 110/50μg o.d. to Fluticasone/Salmeterol 500/50 μg b.i.d | 1.259 liters | Standard Error 0.017 |
| Fluticasone/Salmeterol | Trough Forced Expiratory Volume in One Second (FEV1) Following 26 Weeks of Treatment to Demonstrate the Superiority of QVA 110/50μg o.d. to Fluticasone/Salmeterol 500/50 μg b.i.d | 1.183 liters | Standard Error 0.0168 |