Chronic Obstructive Pulmonary Disease (COPD)
Conditions
Keywords
COPD, QAB149, QVA149, indacaterol maleate, gylcopyrronium bromide
Brief summary
This study is to assess the safety and tolerability of two different doses of QVA149 and QAB149 in patients with moderate to severe airflow limitation.
Interventions
DRUGQVA149
QVA149 will be supplied in a capsule form in blister packs for use in the Novartis Concept1 SDDPI
DRUGQAB149
QAB149 and matching placebo will be supplied in capsule form in blister packs for use in the Novartis Concept1 SDDPI
DRUGPlacebo
To mimic QAB149
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
* Male and female adults aged ≥40 years * Patients with stable COPD according to GOLD strategy (GOLD 2011). * Patients with airflow limitation indicated by a post-bronchodilator FEV1 ≥ 30% and \<80% of the predicted normal, and a post-bronchodilator FEV1/FVC \< 0.70. * Current or ex-smokers who have a smoking history of at least 10 pack years. * Patients with an mMRC ≥ grade 2
Exclusion criteria
* History of long QT syndrome or prolonged QTc * Patients who have had a COPD exacerbation that required treatment with antibiotics and/or systemic corticosteroids and/or hospitalization in the 6 weeks prior to Visit 1. * Patients with Type I or uncontrolled Type II diabetes * Patients with a history of asthma or have concomitant pulmonary disease * Patients with paroxysmal (e.g. intermittent) atrial fibrillation. Only patients with persistent atrial fibrillation and controlled with a rate control strategy for at least six months could be eligible * Patients who have clinically significant renal, cardiovascular, neurological, endocrine, immunological, psychiatric, gastrointestinal, hepatic, or hematological abnormalities which could interfere with the assessment of safety * Other protocol defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Adverse Events, Serious Adverse Events, and Death | 56 weeks | The overall rate of adverse events reported from initiation through 30 days post last dose. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Pre-dose Trough FEV1 | Day 29, 57,, 85, 141, 197, 253, 309 and 365 | Pulmonary function assessments were performed using centralized spirometry according to international standards. Baseline FEV1 was defined as the average of the pre-dose FEV1 measured at -45 minutes (min) and -15 min at day 1. A mixed model for repeated measures (MMRM), used for this analysis, included terms of treatment, baseline FEV1 measurements, smoking status at baseline, baseline inhaled corticosteroid (ICS) use, region, baseline FEV1 \* visit interaction, and visit, treatment \* visit interaction. |
| Change From Baseline in 1 Hour Post-dose FEV1 Measurements | Day 1, 29, 57, 85, 141, 197, 253, 309, and 365 | Pulmonary function assessments were performed using centralized spirometry according to international standards. Baseline FEV1 was defined as the average of the pre-dose FEV1 measured at -45 minutes (min) and -15 min at day 1. A mixed model for repeated measures (MMRM), used for this analysis, included terms of treatment, baseline FEV1 measurements, smoking status at baseline, baseline inhaled corticosteroid (ICS) use, region, baseline FEV1 \* visit interaction, and visit, treatment \* visit interaction. |
| Change From Baseline in FVC Measurement at All Post-baseline Time Points | Day1, 29, 57, 85, 141, 197, 253, 309, and 365 | Pulmonary function assessments were performed using centralized spirometry according to international standards. |
| Time to Premature Discontinuation of Treatment | 56 weeks | methodTime to premature treatment discontinuation for each treatment group was displayed using a Kaplan-Meier curve. The date of last dose of study medication was considered as the event date and also as the censoring date for those patients who did not discontinue treatment earl |
| Change From Baseline in Mean Total Daily Symptom Scores | 52 weeks | The participant recorded symptom scores twice daily in the eDiary. The daily clinical symptoms included: cough, wheezing, shortness of breath, sputum volume, sputum color, and night time awakening. The range of scores for each assessment is 0 to 3 where 0 indications No symptom and 3 indicates a Severe symptom. The maximum daytime total score is 27 and the maximum nighttime total score is 27. The total daily symptom score is obtained by adding the scores for the morning and evening symptoms for each day. The maximum possible total daily score is 54. A negative change from baseline indicated improvement. |
| Change From Baseline in the Daily Number of Puffs of Rescue Medication Over the 52 Week Period | 52 weeks | Participants completed an electronic diary (eDiary) twice daily at the same time in the morning and evening to record the number of puffs of rescue medication taken in the previous 12 hours. |
| Percentage of Participants Experiencing Moderate or Severe COPD Exacerbation | 52 weeks | Percentage of participants experiencing moderate or severe Chronic Obstructive Pulmonary Disease (COPD) |
Countries
Bulgaria, Finland, Hungary, Puerto Rico, Romania, Spain, United States
Participant flow
Recruitment details
Patients were randomized to each treatment arm in 1:1:1 ratio.
Pre-assignment details
Six hundred fifteen patients were randomized. One patient was randomized but did not receive treatment due to an adverse event. In the safety set, patients were analyzed according to the treatment received. Therefore, protocol enrollment and analysis set was 614 but the participant flow was 615
Participants by arm
| Arm | Count |
|---|---|
| QVA149 27.5/12.5 ug Bid | 204 |
| QVA149 27.5/25 ug Bid | 204 |
| QAB149 75 ug od | 207 |
| Total | 615 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 2 |
| Overall Study | Death | 1 | 3 | 4 |
| Overall Study | Lost to Follow-up | 5 | 1 | 6 |
| Overall Study | Physician Decision | 0 | 0 | 1 |
| Overall Study | Protocol deviation | 1 | 0 | 1 |
| Overall Study | Subject/guardian decision | 19 | 12 | 10 |
| Overall Study | Technical problems | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | QVA149 27.5/12.5 ug Bid | QVA149 27.5/25 ug Bid | QAB149 75 ug od | Total |
|---|---|---|---|---|
| Age, Continuous | 64.0 Years STANDARD_DEVIATION 7.9 | 63.9 Years STANDARD_DEVIATION 8.5 | 62.8 Years STANDARD_DEVIATION 8.52 | 63.6 Years STANDARD_DEVIATION 8.32 |
| Sex: Female, Male Female | 73 Participants | 81 Participants | 58 Participants | 212 Participants |
| Sex: Female, Male Male | 131 Participants | 123 Participants | 149 Participants | 403 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 118 / 204 | 117 / 204 | 112 / 206 |
| serious Total, serious adverse events | 26 / 204 | 25 / 204 | 24 / 206 |
Outcome results
Primary
Number of Patients With Adverse Events, Serious Adverse Events, and Death
The overall rate of adverse events reported from initiation through 30 days post last dose.
Time frame: 56 weeks
Population: The Safety set:all patients that received at least one dose of study medication and had at least one post-baseline safety assessment. Patients were analyzed according to treatment received. The statement that a patient had no AEs also constituted a safety assessment. Only deaths occurring on treatment + 30 days after end of treatment were included.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| QVA149 27.5/12.5 ug Bid | Number of Patients With Adverse Events, Serious Adverse Events, and Death | Patients with at least one AE | 139 Number of Patients |
| QVA149 27.5/12.5 ug Bid | Number of Patients With Adverse Events, Serious Adverse Events, and Death | Patients with at least one SAEs | 26 Number of Patients |
| QVA149 27.5/12.5 ug Bid | Number of Patients With Adverse Events, Serious Adverse Events, and Death | Death | 1 Number of Patients |
| QVA149 27.5/25 ug Bid | Number of Patients With Adverse Events, Serious Adverse Events, and Death | Patients with at least one AE | 142 Number of Patients |
| QVA149 27.5/25 ug Bid | Number of Patients With Adverse Events, Serious Adverse Events, and Death | Patients with at least one SAEs | 25 Number of Patients |
| QVA149 27.5/25 ug Bid | Number of Patients With Adverse Events, Serious Adverse Events, and Death | Death | 3 Number of Patients |
| QAB149 75 ug od | Number of Patients With Adverse Events, Serious Adverse Events, and Death | Patients with at least one SAEs | 24 Number of Patients |
| QAB149 75 ug od | Number of Patients With Adverse Events, Serious Adverse Events, and Death | Death | 5 Number of Patients |
| QAB149 75 ug od | Number of Patients With Adverse Events, Serious Adverse Events, and Death | Patients with at least one AE | 139 Number of Patients |
Secondary
Change From Baseline in 1 Hour Post-dose FEV1 Measurements
Pulmonary function assessments were performed using centralized spirometry according to international standards. Baseline FEV1 was defined as the average of the pre-dose FEV1 measured at -45 minutes (min) and -15 min at day 1. A mixed model for repeated measures (MMRM), used for this analysis, included terms of treatment, baseline FEV1 measurements, smoking status at baseline, baseline inhaled corticosteroid (ICS) use, region, baseline FEV1 \* visit interaction, and visit, treatment \* visit interaction.
Time frame: Day 1, 29, 57, 85, 141, 197, 253, 309, and 365
Population: The Full Analysis set (FAS) included all randomized patients who received at least one dose of study medication. Participants, who had both baseline and week 52 values, were included in the analysis. Patients were analyzed according to the treatment to which they were randomized.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| QVA149 27.5/12.5 ug Bid | Change From Baseline in 1 Hour Post-dose FEV1 Measurements | Day 85 | 0.269 Liters | Standard Error 0.0164 |
| QVA149 27.5/12.5 ug Bid | Change From Baseline in 1 Hour Post-dose FEV1 Measurements | Day 365 | 0.212 Liters | Standard Error 0.0175 |
| QVA149 27.5/12.5 ug Bid | Change From Baseline in 1 Hour Post-dose FEV1 Measurements | Day 197 | 0.229 Liters | Standard Error 0.0178 |
| QVA149 27.5/12.5 ug Bid | Change From Baseline in 1 Hour Post-dose FEV1 Measurements | Day 141 | 0.268 Liters | Standard Error 0.0182 |
| QVA149 27.5/12.5 ug Bid | Change From Baseline in 1 Hour Post-dose FEV1 Measurements | Day 1 | 0.166 Liters | Standard Error 0.0088 |
| QVA149 27.5/12.5 ug Bid | Change From Baseline in 1 Hour Post-dose FEV1 Measurements | Day 309 | 0.199 Liters | Standard Error 0.017 |
| QVA149 27.5/12.5 ug Bid | Change From Baseline in 1 Hour Post-dose FEV1 Measurements | Day 57 | 0.267 Liters | Standard Error 0.0157 |
| QVA149 27.5/12.5 ug Bid | Change From Baseline in 1 Hour Post-dose FEV1 Measurements | Day 29 | 0.257 Liters | Standard Error 0.0152 |
| QVA149 27.5/12.5 ug Bid | Change From Baseline in 1 Hour Post-dose FEV1 Measurements | Day 253 | 0.231 Liters | Standard Error 0.0178 |
| QVA149 27.5/25 ug Bid | Change From Baseline in 1 Hour Post-dose FEV1 Measurements | Day 141 | 0.288 Liters | Standard Error 0.0179 |
| QVA149 27.5/25 ug Bid | Change From Baseline in 1 Hour Post-dose FEV1 Measurements | Day 1 | 0.178 Liters | Standard Error 0.0088 |
| QVA149 27.5/25 ug Bid | Change From Baseline in 1 Hour Post-dose FEV1 Measurements | Day 29 | 0.287 Liters | Standard Error 0.0151 |
| QVA149 27.5/25 ug Bid | Change From Baseline in 1 Hour Post-dose FEV1 Measurements | Day 57 | 0.302 Liters | Standard Error 0.0155 |
| QVA149 27.5/25 ug Bid | Change From Baseline in 1 Hour Post-dose FEV1 Measurements | Day 85 | 0.301 Liters | Standard Error 0.0162 |
| QVA149 27.5/25 ug Bid | Change From Baseline in 1 Hour Post-dose FEV1 Measurements | Day 197 | 0.278 Liters | Standard Error 0.0175 |
| QVA149 27.5/25 ug Bid | Change From Baseline in 1 Hour Post-dose FEV1 Measurements | Day 253 | 0.240 Liters | Standard Error 0.0175 |
| QVA149 27.5/25 ug Bid | Change From Baseline in 1 Hour Post-dose FEV1 Measurements | Day 309 | 0.222 Liters | Standard Error 0.0169 |
| QVA149 27.5/25 ug Bid | Change From Baseline in 1 Hour Post-dose FEV1 Measurements | Day 365 | 0.221 Liters | Standard Error 0.0173 |
| QAB149 75 ug od | Change From Baseline in 1 Hour Post-dose FEV1 Measurements | Day 57 | 0.173 Liters | Standard Error 0.0154 |
| QAB149 75 ug od | Change From Baseline in 1 Hour Post-dose FEV1 Measurements | Day 1 | 0.122 Liters | Standard Error 0.0089 |
| QAB149 75 ug od | Change From Baseline in 1 Hour Post-dose FEV1 Measurements | Day 253 | 0.140 Liters | Standard Error 0.0176 |
| QAB149 75 ug od | Change From Baseline in 1 Hour Post-dose FEV1 Measurements | Day 29 | 0.173 Liters | Standard Error 0.0151 |
| QAB149 75 ug od | Change From Baseline in 1 Hour Post-dose FEV1 Measurements | Day 365 | 0.104 Liters | Standard Error 0.0174 |
| QAB149 75 ug od | Change From Baseline in 1 Hour Post-dose FEV1 Measurements | Day 141 | 0.170 Liters | Standard Error 0.0181 |
| QAB149 75 ug od | Change From Baseline in 1 Hour Post-dose FEV1 Measurements | Day 85 | 0.170 Liters | Standard Error 0.0162 |
| QAB149 75 ug od | Change From Baseline in 1 Hour Post-dose FEV1 Measurements | Day 309 | 0.125 Liters | Standard Error 0.017 |
| QAB149 75 ug od | Change From Baseline in 1 Hour Post-dose FEV1 Measurements | Day 197 | 0.157 Liters | Standard Error 0.0177 |
Secondary
Change From Baseline in FVC Measurement at All Post-baseline Time Points
Pulmonary function assessments were performed using centralized spirometry according to international standards.
Time frame: Day1, 29, 57, 85, 141, 197, 253, 309, and 365
Population: The Full Analysis set (FAS) included all randomized patients who received at least one dose of study medication. Participants, who had both baseline and week 52 values, were included in the analysis. Patients were analyzed according to the treatment to which they were randomized.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| QVA149 27.5/12.5 ug Bid | Change From Baseline in FVC Measurement at All Post-baseline Time Points | Day 85 | 0.388 Liters | Standard Error 0.0287 |
| QVA149 27.5/12.5 ug Bid | Change From Baseline in FVC Measurement at All Post-baseline Time Points | Day 365 | 0.312 Liters | Standard Error 0.0286 |
| QVA149 27.5/12.5 ug Bid | Change From Baseline in FVC Measurement at All Post-baseline Time Points | Day 197 | 0.313 Liters | Standard Error 0.0288 |
| QVA149 27.5/12.5 ug Bid | Change From Baseline in FVC Measurement at All Post-baseline Time Points | Day 141 | 0.382 Liters | Standard Error 0.0297 |
| QVA149 27.5/12.5 ug Bid | Change From Baseline in FVC Measurement at All Post-baseline Time Points | Day 1 | 0.316 Liters | Standard Error 0.0201 |
| QVA149 27.5/12.5 ug Bid | Change From Baseline in FVC Measurement at All Post-baseline Time Points | Day 309 | 0.272 Liters | Standard Error 0.0284 |
| QVA149 27.5/12.5 ug Bid | Change From Baseline in FVC Measurement at All Post-baseline Time Points | Day 57 | 0.390 Liters | Standard Error 0.0274 |
| QVA149 27.5/12.5 ug Bid | Change From Baseline in FVC Measurement at All Post-baseline Time Points | Day 29 | 0.375 Liters | Standard Error 0.0274 |
| QVA149 27.5/12.5 ug Bid | Change From Baseline in FVC Measurement at All Post-baseline Time Points | Day 253 | 0.310 Liters | Standard Error 0.0303 |
| QVA149 27.5/25 ug Bid | Change From Baseline in FVC Measurement at All Post-baseline Time Points | Day 141 | 0.403 Liters | Standard Error 0.0292 |
| QVA149 27.5/25 ug Bid | Change From Baseline in FVC Measurement at All Post-baseline Time Points | Day 1 | 0.349 Liters | Standard Error 0.02 |
| QVA149 27.5/25 ug Bid | Change From Baseline in FVC Measurement at All Post-baseline Time Points | Day 29 | 0.440 Liters | Standard Error 0.0271 |
| QVA149 27.5/25 ug Bid | Change From Baseline in FVC Measurement at All Post-baseline Time Points | Day 57 | 0.439 Liters | Standard Error 0.0271 |
| QVA149 27.5/25 ug Bid | Change From Baseline in FVC Measurement at All Post-baseline Time Points | Day 85 | 0.432 Liters | Standard Error 0.0283 |
| QVA149 27.5/25 ug Bid | Change From Baseline in FVC Measurement at All Post-baseline Time Points | Day 197 | 0.400 Liters | Standard Error 0.0284 |
| QVA149 27.5/25 ug Bid | Change From Baseline in FVC Measurement at All Post-baseline Time Points | Day 253 | 0.365 Liters | Standard Error 0.0298 |
| QVA149 27.5/25 ug Bid | Change From Baseline in FVC Measurement at All Post-baseline Time Points | Day 309 | 0.334 Liters | Standard Error 0.0281 |
| QVA149 27.5/25 ug Bid | Change From Baseline in FVC Measurement at All Post-baseline Time Points | Day 365 | 0.323 Liters | Standard Error 0.0282 |
| QAB149 75 ug od | Change From Baseline in FVC Measurement at All Post-baseline Time Points | Day 57 | 0.279 Liters | Standard Error 0.0271 |
| QAB149 75 ug od | Change From Baseline in FVC Measurement at All Post-baseline Time Points | Day 1 | 0.248 Liters | Standard Error 0.0203 |
| QAB149 75 ug od | Change From Baseline in FVC Measurement at All Post-baseline Time Points | Day 253 | 0.205 Liters | Standard Error 0.0301 |
| QAB149 75 ug od | Change From Baseline in FVC Measurement at All Post-baseline Time Points | Day 29 | 0.280 Liters | Standard Error 0.0272 |
| QAB149 75 ug od | Change From Baseline in FVC Measurement at All Post-baseline Time Points | Day 365 | 0.139 Liters | Standard Error 0.0286 |
| QAB149 75 ug od | Change From Baseline in FVC Measurement at All Post-baseline Time Points | Day 141 | 0.235 Liters | Standard Error 0.0295 |
| QAB149 75 ug od | Change From Baseline in FVC Measurement at All Post-baseline Time Points | Day 85 | 0.268 Liters | Standard Error 0.0284 |
| QAB149 75 ug od | Change From Baseline in FVC Measurement at All Post-baseline Time Points | Day 309 | 0.185 Liters | Standard Error 0.0285 |
| QAB149 75 ug od | Change From Baseline in FVC Measurement at All Post-baseline Time Points | Day 197 | 0.220 Liters | Standard Error 0.0288 |
Secondary
Change From Baseline in Mean Total Daily Symptom Scores
The participant recorded symptom scores twice daily in the eDiary. The daily clinical symptoms included: cough, wheezing, shortness of breath, sputum volume, sputum color, and night time awakening. The range of scores for each assessment is 0 to 3 where 0 indications No symptom and 3 indicates a Severe symptom. The maximum daytime total score is 27 and the maximum nighttime total score is 27. The total daily symptom score is obtained by adding the scores for the morning and evening symptoms for each day. The maximum possible total daily score is 54. A negative change from baseline indicated improvement.
Time frame: 52 weeks
Population: The Full Analysis set (FAS) included all randomized patients who received at least one dose of study medication. Participants, who had both baseline and week 52 values, were included in the analysis. Patients were analyzed according to the treatment to which they were randomized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| QVA149 27.5/12.5 ug Bid | Change From Baseline in Mean Total Daily Symptom Scores | -1.57 Score on a scale | Standard Error 0.133 |
| QVA149 27.5/25 ug Bid | Change From Baseline in Mean Total Daily Symptom Scores | -1.56 Score on a scale | Standard Error 0.133 |
| QAB149 75 ug od | Change From Baseline in Mean Total Daily Symptom Scores | -1.31 Score on a scale | Standard Error 0.135 |
Secondary
Change From Baseline in Pre-dose Trough FEV1
Pulmonary function assessments were performed using centralized spirometry according to international standards. Baseline FEV1 was defined as the average of the pre-dose FEV1 measured at -45 minutes (min) and -15 min at day 1. A mixed model for repeated measures (MMRM), used for this analysis, included terms of treatment, baseline FEV1 measurements, smoking status at baseline, baseline inhaled corticosteroid (ICS) use, region, baseline FEV1 \* visit interaction, and visit, treatment \* visit interaction.
Time frame: Day 29, 57,, 85, 141, 197, 253, 309 and 365
Population: The Full Analysis set (FAS) included all randomized patients who received at least one dose of study medication. Participants, who had both baseline and week 52 values, were included in the analysis. Patients were analyzed according to the treatment to which they were randomized.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| QVA149 27.5/12.5 ug Bid | Change From Baseline in Pre-dose Trough FEV1 | Day 29 | 0.164 Liters | Standard Error 0.0144 |
| QVA149 27.5/12.5 ug Bid | Change From Baseline in Pre-dose Trough FEV1 | Day 57 | 0.178 Liters | Standard Error 0.0151 |
| QVA149 27.5/12.5 ug Bid | Change From Baseline in Pre-dose Trough FEV1 | Day 85 | 0.166 Liters | Standard Error 0.0158 |
| QVA149 27.5/12.5 ug Bid | Change From Baseline in Pre-dose Trough FEV1 | Day 141 | 0.174 Liters | Standard Error 0.0173 |
| QVA149 27.5/12.5 ug Bid | Change From Baseline in Pre-dose Trough FEV1 | Day 197 | 0.138 Liters | Standard Error 0.0167 |
| QVA149 27.5/12.5 ug Bid | Change From Baseline in Pre-dose Trough FEV1 | Day 253 | 0.142 Liters | Standard Error 0.0168 |
| QVA149 27.5/12.5 ug Bid | Change From Baseline in Pre-dose Trough FEV1 | Day 309 | 0.096 Liters | Standard Error 0.0162 |
| QVA149 27.5/12.5 ug Bid | Change From Baseline in Pre-dose Trough FEV1 | Day 365 | 0.116 Liters | Standard Error 0.0169 |
| QVA149 27.5/25 ug Bid | Change From Baseline in Pre-dose Trough FEV1 | Day 85 | 0.201 Liters | Standard Error 0.0157 |
| QVA149 27.5/25 ug Bid | Change From Baseline in Pre-dose Trough FEV1 | Day 309 | 0.123 Liters | Standard Error 0.0161 |
| QVA149 27.5/25 ug Bid | Change From Baseline in Pre-dose Trough FEV1 | Day 141 | 0.198 Liters | Standard Error 0.017 |
| QVA149 27.5/25 ug Bid | Change From Baseline in Pre-dose Trough FEV1 | Day 197 | 0.181 Liters | Standard Error 0.0165 |
| QVA149 27.5/25 ug Bid | Change From Baseline in Pre-dose Trough FEV1 | Day 253 | 0.153 Liters | Standard Error 0.0165 |
| QVA149 27.5/25 ug Bid | Change From Baseline in Pre-dose Trough FEV1 | Day 29 | 0.194 Liters | Standard Error 0.0143 |
| QVA149 27.5/25 ug Bid | Change From Baseline in Pre-dose Trough FEV1 | Day 57 | 0.199 Liters | Standard Error 0.0149 |
| QVA149 27.5/25 ug Bid | Change From Baseline in Pre-dose Trough FEV1 | Day 365 | 0.116 Liters | Standard Error 0.0167 |
| QAB149 75 ug od | Change From Baseline in Pre-dose Trough FEV1 | Day 85 | 0.095 Liters | Standard Error 0.0157 |
| QAB149 75 ug od | Change From Baseline in Pre-dose Trough FEV1 | Day 57 | 0.107 Liters | Standard Error 0.0149 |
| QAB149 75 ug od | Change From Baseline in Pre-dose Trough FEV1 | Day 29 | 0.109 Liters | Standard Error 0.0143 |
| QAB149 75 ug od | Change From Baseline in Pre-dose Trough FEV1 | Day 141 | 0.087 Liters | Standard Error 0.0171 |
| QAB149 75 ug od | Change From Baseline in Pre-dose Trough FEV1 | Day 309 | 0.050 Liters | Standard Error 0.0162 |
| QAB149 75 ug od | Change From Baseline in Pre-dose Trough FEV1 | Day 253 | 0.074 Liters | Standard Error 0.0167 |
| QAB149 75 ug od | Change From Baseline in Pre-dose Trough FEV1 | Day 197 | 0.079 Liters | Standard Error 0.0166 |
| QAB149 75 ug od | Change From Baseline in Pre-dose Trough FEV1 | Day 365 | 0.037 Liters | Standard Error 0.0169 |
Secondary
Change From Baseline in the Daily Number of Puffs of Rescue Medication Over the 52 Week Period
Participants completed an electronic diary (eDiary) twice daily at the same time in the morning and evening to record the number of puffs of rescue medication taken in the previous 12 hours.
Time frame: 52 weeks
Population: The Full Analysis set (FAS) included all randomized patients who received at least one dose of study medication. Participants, who had both baseline and week 52 values, were included in the analysis. Patients were analyzed according to the treatment to which they were randomized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| QVA149 27.5/12.5 ug Bid | Change From Baseline in the Daily Number of Puffs of Rescue Medication Over the 52 Week Period | -1.89 Number of puffs | Standard Error 0.164 |
| QVA149 27.5/25 ug Bid | Change From Baseline in the Daily Number of Puffs of Rescue Medication Over the 52 Week Period | -1.62 Number of puffs | Standard Error 0.164 |
| QAB149 75 ug od | Change From Baseline in the Daily Number of Puffs of Rescue Medication Over the 52 Week Period | -1.73 Number of puffs | Standard Error 0.166 |
Secondary
Percentage of Participants Experiencing Moderate or Severe COPD Exacerbation
Percentage of participants experiencing moderate or severe Chronic Obstructive Pulmonary Disease (COPD)
Time frame: 52 weeks
Population: The Full Analysis set (FAS) included all randomized patients who received at least one dose of study medication. Participants, who had both baseline and week 52 values, were included in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| QVA149 27.5/12.5 ug Bid | Percentage of Participants Experiencing Moderate or Severe COPD Exacerbation | 23.5 Percentage of participants |
| QVA149 27.5/25 ug Bid | Percentage of Participants Experiencing Moderate or Severe COPD Exacerbation | 24.9 Percentage of participants |
| QAB149 75 ug od | Percentage of Participants Experiencing Moderate or Severe COPD Exacerbation | 27.0 Percentage of participants |
Secondary
Time to Premature Discontinuation of Treatment
methodTime to premature treatment discontinuation for each treatment group was displayed using a Kaplan-Meier curve. The date of last dose of study medication was considered as the event date and also as the censoring date for those patients who did not discontinue treatment earl
Time frame: 56 weeks
Population: The Safety set consisted of all patients that received at least one dose of study medication and had at least one post-baseline safety assessment. Patients were analyzed according to treatment received.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| QVA149 27.5/12.5 ug Bid | Time to Premature Discontinuation of Treatment | 384.0 Days | 95% Confidence Interval 0.164 |
| QVA149 27.5/25 ug Bid | Time to Premature Discontinuation of Treatment | NA Days | 95% Confidence Interval 0.164 |
| QAB149 75 ug od | Time to Premature Discontinuation of Treatment | NA Days | 95% Confidence Interval 0.166 |