COPD
Conditions
Brief summary
This study will investigate whether switching symptomatic COPD patients from a fixed-dose combination of salmeterol/fluticasone 50/500 µg b.i.d. to a fixed dose combination of QVA149 110/50 µg o.d. leads to improved lung function and airflow. It will also assess the effect on symptom burden, breathlessness, and use of rescue medication after this switch.
Interventions
DRUGQVA149 110/50 micrograms
QVA149 110/50 micrograms o.d. capsules for inhalation, supplied in blisters via a single dose dry powder inhalater (SDDPI)
DRUGSalmeterol/fluticasone 50/500 microgrammes
Salmeterol/fluticasone 50/500 microgrammes b.i.d.dry inhalation powder delivered via Accuhaler / Diskus device
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
* Written informed consent must be obtained before any assessment is performed. * Male and female ≥ 40 years * Current or ex-smokers who have a smoking history of at least 10 pack years (Ten pack years are defined as 20 cigarettes per day for 10 years or 10 cigarettes per day for 20 years). An ex-smoker is defined as a patient who has not smoked for ≥ 6 months at visit 1 * Confirmed diagnosis of COPD and post-bronchodilator FEV1 ≥ 30% and \< 80% of the predicted normal value and post-bronchodilator FEV1/FVC \< 0.70 at visit 1 * Treated with salmeterol/fluticasone 50/500 µg b.i.d. for at least 3 months prior to visit 1 * Documented CAT score of ≥ 10 at Visit 1 and 2
Exclusion criteria
* Treatment with any LAMA in the 2 weeks prior to visit 1 * Presence of any contraindication, warning, precaution, hypersensitivity in the approved prescribing information for salmeterol/fluticasone * Prior or current diagnosis of asthma * More than one COPD exacerbation requiring treatment with antibiotics and/or systemic corticosteroids and/or hospitalization in the year prior to Visit 1 * Patients who developed a COPD exacerbation of any severity within the 6 weeks before the screening (Visit 1) or between screening (Visit 1) and start of treatment (Visit 2) will not be eligible but will be permitted to be re-screened after a minimum of 6 weeks after the resolution of the COPD exacerbation * Respiratory tract infection within 4 weeks prior to Visit 1 * Respiratory tract infection between Visit 1 and 2. Patients can be re-screened 4 weeks after resolution of the infection * Requiring oxygen therapy prescribed for \>12 hours per day * Onset of respiratory symptoms, including a COPD diagnosis prior to age 40 years
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Trough Pre-dose FEV1 in Both Arms | Baseline, week 12 | Pulmonary function assessments were performed using centralized spirometry according to international standards. Mean trough pre-dose FEV1 at Week 12 is defined as the average of the measurements taken -45min and -15min pre study medication dose in the clinic after 12 weeks of treatment (Day 84). The baseline measurement is defined as the average of the scheduled FEV1 values prior to first intake of randomized study drug at Day 1 (Visit 2). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Transitional Dyspnea Index (TDI) Focal Score | Baseline, week 12 | Transition Dyspnea Index (TDI) is an instrument used to assess a participant's level of dyspnea. The TDI focal score have three domains: functional impairment, magnitude of task and magnitude of effort. TDI domains were rated from -3 (major deterioration) to 3 (major improvement) and rates summed for transition focal score ranged from -9 to 9; negative scores indicate deterioration. A TDI focal score of ≥1 was defined as a clinically important improvement from baseline. |
| Change From Baseline in FVC (Forced Vital Capacity) | week 12 | Pulmonary function assessments were performed using centralized spirometry according to international standards. FVC wil follow the same analysis as for FEV1 |
| Change From Baseline in Total Symptom Score- CAT (COPD Assessment Test) | week 12 | The participants will record their COPD symptoms in this test before every clinic visit, this will include : cough, phlegm, chest tightness, breathlessness, limitation in activities, energy, soundly sleep, etc. A higher score indicates a worse health status. The result is immediately available without the need for any calculation, apart from summing the scores on individual items. Scores of 0 - 10 represent mild, 11 - 20 represent moderate, 21 - 30 represent severe and 31 - 40 represent very severe clinical impact of COPD upon the patient. |
| Change From Baseline in Mean Daily Use of Rescue Medication | over 12 weeks | Use of rescue medication (number of puffs taken in the previous 12 hours) is recorded morning and evening, by the patient, in a paper diary. A negative change from baseline indicates an improvement. |
Countries
Australia, Egypt, India, Israel, Lebanon, Malaysia, Philippines, Saudi Arabia, South Africa, Taiwan, Turkey (Türkiye)
Participant flow
Recruitment details
A total of 502 patients were randomized, of which 498 patients were included in the Full Analysis Set (FAS)
Participants by arm
| Arm | Count |
|---|---|
| QVA149 110/50 Micrograms QVA149 110/50 micrograms o.d. Capsules for inhalation | 251 |
| Salmeterol/Fluticasone 50/500 Micrograms salmeterol/fluticasone 50/500 micrograms b.i.d. Dry inhalation powder | 251 |
| Total | 502 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Abnormal test procedure result | 1 | 0 |
| Overall Study | Adverse Event | 1 | 2 |
| Overall Study | Death | 1 | 1 |
| Overall Study | Lost to Follow-up | 2 | 3 |
| Overall Study | Patient/guardian decision | 2 | 1 |
| Overall Study | Patient withdrew consent | 5 | 2 |
| Overall Study | Protocol deviation | 4 | 4 |
Baseline characteristics
| Characteristic | Salmeterol/Fluticasone 50/500 Micrograms | Total | QVA149 110/50 Micrograms |
|---|---|---|---|
| Age, Continuous | 65.1 Years STANDARD_DEVIATION 8.44 | 65 Years STANDARD_DEVIATION 8.79 | 65 Years STANDARD_DEVIATION 9.14 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 118 Participants | 233 Participants | 115 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 2 Participants | 2 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 | 6 Participants | 14 Participants | 8 Participants |
| Race (NIH/OMB) White | 126 Participants | 249 Participants | 123 Participants |
| Sex: Female, Male Female | 26 Participants | 54 Participants | 28 Participants |
| Sex: Female, Male Male | 224 Participants | 444 Participants | 220 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 248 | 1 / 250 |
| other Total, other adverse events | 39 / 248 | 50 / 250 |
| serious Total, serious adverse events | 9 / 248 | 9 / 250 |
Outcome results
Primary
Change From Baseline in Trough Pre-dose FEV1 in Both Arms
Pulmonary function assessments were performed using centralized spirometry according to international standards. Mean trough pre-dose FEV1 at Week 12 is defined as the average of the measurements taken -45min and -15min pre study medication dose in the clinic after 12 weeks of treatment (Day 84). The baseline measurement is defined as the average of the scheduled FEV1 values prior to first intake of randomized study drug at Day 1 (Visit 2).
Time frame: Baseline, week 12
Population: The full analysis set (FAS) included all randomized patients who received at least one dose of randomized study medication; patients were analyzed according to the treatment they were randomized to
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| QVA149 110/50 Micrograms | Change From Baseline in Trough Pre-dose FEV1 in Both Arms | 0.036 Liters | Standard Error 0.0151 |
| Salmeterol/Fluticasone 50/500 Micrograms | Change From Baseline in Trough Pre-dose FEV1 in Both Arms | -0.009 Liters | Standard Error 0.0152 |
p-value: 0.02895% CI: [0.005, 0.084]Mixed Models Analysis
Secondary
Change From Baseline in FVC (Forced Vital Capacity)
Pulmonary function assessments were performed using centralized spirometry according to international standards. FVC wil follow the same analysis as for FEV1
Time frame: week 12
Population: The full analysis set (FAS) included all randomized patients who received at least one dose of randomized study medication; patients were analyzed according to the treatment they were randomized to
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| QVA149 110/50 Micrograms | Change From Baseline in FVC (Forced Vital Capacity) | 0.073 Liters | Standard Error 0.0248 |
| Salmeterol/Fluticasone 50/500 Micrograms | Change From Baseline in FVC (Forced Vital Capacity) | -0.028 Liters | Standard Error 0.025 |
p-value: 0.00295% CI: [0.037, 0.167]Mixed Models Analysis
Secondary
Change From Baseline in Mean Daily Use of Rescue Medication
Use of rescue medication (number of puffs taken in the previous 12 hours) is recorded morning and evening, by the patient, in a paper diary. A negative change from baseline indicates an improvement.
Time frame: over 12 weeks
Population: The full analysis set (FAS) included all randomized patients who received at least one dose of randomized study medication; patients were analyzed according to the treatment they were randomized to
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| QVA149 110/50 Micrograms | Change From Baseline in Mean Daily Use of Rescue Medication | 1.05 Number of puffs | Standard Error 0.132 |
| Salmeterol/Fluticasone 50/500 Micrograms | Change From Baseline in Mean Daily Use of Rescue Medication | 1.09 Number of puffs | Standard Error 0.13 |
p-value: 0.66295% CI: [-0.2, 0.13]Mixed Models Analysis
Secondary
Change From Baseline in Total Symptom Score- CAT (COPD Assessment Test)
The participants will record their COPD symptoms in this test before every clinic visit, this will include : cough, phlegm, chest tightness, breathlessness, limitation in activities, energy, soundly sleep, etc. A higher score indicates a worse health status. The result is immediately available without the need for any calculation, apart from summing the scores on individual items. Scores of 0 - 10 represent mild, 11 - 20 represent moderate, 21 - 30 represent severe and 31 - 40 represent very severe clinical impact of COPD upon the patient.
Time frame: week 12
Population: The full analysis set (FAS) included all randomized patients who received at least one dose of randomized study medication; patients were analyzed according to the treatment they were randomized to
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| QVA149 110/50 Micrograms | Change From Baseline in Total Symptom Score- CAT (COPD Assessment Test) | 13.4 Score on a scale | Standard Error 0.48 |
| Salmeterol/Fluticasone 50/500 Micrograms | Change From Baseline in Total Symptom Score- CAT (COPD Assessment Test) | 13.8 Score on a scale | Standard Error 0.47 |
p-value: 0.31995% CI: [-1.3, 0.4]Mixed Models Analysis
Secondary
Transitional Dyspnea Index (TDI) Focal Score
Transition Dyspnea Index (TDI) is an instrument used to assess a participant's level of dyspnea. The TDI focal score have three domains: functional impairment, magnitude of task and magnitude of effort. TDI domains were rated from -3 (major deterioration) to 3 (major improvement) and rates summed for transition focal score ranged from -9 to 9; negative scores indicate deterioration. A TDI focal score of ≥1 was defined as a clinically important improvement from baseline.
Time frame: Baseline, week 12
Population: The full analysis set (FAS) included all randomized patients who received at least one dose of randomized study medication; patients were analyzed according to the treatment they were randomized to.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| QVA149 110/50 Micrograms | Transitional Dyspnea Index (TDI) Focal Score | 3.24 Score on a scale | Standard Error 0.405 |
| Salmeterol/Fluticasone 50/500 Micrograms | Transitional Dyspnea Index (TDI) Focal Score | 2.79 Score on a scale | Standard Error 0.399 |
p-value: 0.06395% CI: [-0.03, 0.94]Mixed Models Analysis