COPD
Conditions
Keywords
COPD, open-label, QVA149, symptomatic, tiotropium
Brief summary
To demonstrate superiority of QVA149 (110/50 μg) once daily compared to tiotropium 18 μg once daily in terms of trough forced expiratory volume in 1 second (FEV1) (mean of 45 min and 15 min pre-dose) following 12 weeks of treatment in mild to moderate symptomatic COPD patients
Interventions
Capsules for inhalation delivered via SDDPI
DRUGTiotropium
Capsules for inhalation delivered via HandiHaler® device
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Confirmed diagnosis of COPD and post-bronchodilator FEV1 ≥ 50% of the predicted normal value and post-bronchodilator FEV1/FVC \< 0.7 (COPD Grade 1 or 2 by severity of airflow limitation (GOLD 2015) * Patients with CAT score ≥ 10 at Visit 0 and Visit 1. * Patients who are on and have been on tiotropium monotherapy for the past 3 months. * 0 or 1 COPD exacerbation in the previous 12 months (not leading to hospital admission).
Exclusion criteria
* Treatment with any inhaled corticosteroid (ICS) in the 3 months prior to Visit 1. * COPD exacerbation between Visit 0 and 1. * Patients with concomitant pulmonary disease * Patients with a history of respiratory infection within 4 weeks prior to Visit 0. * Prior or current diagnosis of asthma. * Presence of any contraindication, warning, precaution, hypersensitivity to LABA and LAMA Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Trough Forced Expiratory Volume In One Second (FEV1) After 12 Weeks of Treatment | Week 12 | Spirometry was performed according to internationally accepted standards. Trough FEV1 is defined as the mean of 45 minute and 15 minute pre-dose values. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Trough Forced Expiratory Volume In One Second (FEV1) After 4 Weeks of Treatment | mean of 45 min and 15 min pre-dose week 4 | Spirometry was performed according to internationally accepted standards. Trough FEV1 was defined as the mean of 45 minute and 15 minute pre-dose values. |
| Baseline Transitional Dyspnea Index (TDI) Focal Score | Week 12 | A trained assessor interviewed the patient and graded the degree of impairment due to dyspnea (difficulty breathing). TDI focal score is based on three domains: functional impairment, magnitude of task and magnitude of effort and captures changes from baseline. TDI captures changes from baseline, each domain is scored from -3=major deterioration to 3=major improvement to give an overall TDI focal score of -9 to 9. Higher numbers indicate a better score. |
| Number of Participants With Change From Baseline on Total Score of COPD Assessment Test (CAT) | Week 12 | Total score of COPD Assessment Test (CAT) will be measured at week 12. This questionnaire is completed by the patient. The score ranges from 0-40 where higher scores represent worse health status. Mild: Score = 0 - 10, Moderate: Score = 11 - 20, Severe: Score = 21 - 30, Very Severe: Score = 31 - 40. The CAT total score was the sum of 8 item scores (each ranging from 0 to 5). If 1 or 2 items were missing, they were replaced with the mean of the completed items. If 3 or more items were missing, the CAT total score was set missing |
| Daily Rescue Medication Use (Number of Puffs) | Week 12 | The total number of puffs of rescue medication used over the last 24 hours will be recorded in the patient diary in the morning. The total number of puffs of rescue medication per day over the full 12 weeks will be calculated and divided by the total number of days with non-missing rescue medication data to derive the mean daily number of puffs of rescue medication taken for the patient. The mean daily number of puffs of rescue medication used over 12 weeks will be summarized by treatments |
Countries
South Korea
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Indacaterol and Glycopyrronium (QVA149) QVA149 110/50 μg capsules for inhalation delivered once daily via single-dose dry powder inhaler (SDPPI) for 12 weeks | 189 |
| Tiotropium Tiotropium 18 μg capsules for inhalation delivered once daily via HandiHaler® device for 12 weeks | 190 |
| Total | 379 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 1 |
| Overall Study | Lost to Follow-up | 1 | 1 |
| Overall Study | Patient/guardian decision | 14 | 7 |
| Overall Study | Protocol deviation | 2 | 3 |
Baseline characteristics
| Characteristic | Tiotropium | Total | Indacaterol and Glycopyrronium (QVA149) |
|---|---|---|---|
| Age, Continuous | 69.0 Years STANDARD_DEVIATION 7.54 | 69.1 Years STANDARD_DEVIATION 7.81 | 69.2 Years STANDARD_DEVIATION 8.08 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 190 Participants | 379 Participants | 189 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 | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 7 Participants | 10 Participants | 3 Participants |
| Sex: Female, Male Male | 183 Participants | 369 Participants | 186 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 189 | 0 / 188 | 0 / 377 |
| other Total, other adverse events | 12 / 189 | 9 / 188 | 21 / 377 |
| serious Total, serious adverse events | 8 / 189 | 3 / 188 | 11 / 377 |
Outcome results
Primary
Trough Forced Expiratory Volume In One Second (FEV1) After 12 Weeks of Treatment
Spirometry was performed according to internationally accepted standards. Trough FEV1 is defined as the mean of 45 minute and 15 minute pre-dose values.
Time frame: Week 12
Population: The full analysis set (FAS) consisted of all randomized patients who received at least one dose of study treatment and have at least one evaluable post-baseline assessment.~Following the intent-to-treat principle, patients were analyzed according to the treatment they were assigned to at randomization
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Indacaterol and Glycopyrronium (QVA149) | Trough Forced Expiratory Volume In One Second (FEV1) After 12 Weeks of Treatment | 0.0668 Liters | Standard Deviation 0.18097 |
| Tiotropium | Trough Forced Expiratory Volume In One Second (FEV1) After 12 Weeks of Treatment | 0.0090 Liters | Standard Deviation 0.18487 |
p-value: 0.012995% CI: [0.011, 0.093]ANCOVA
Secondary
Baseline Transitional Dyspnea Index (TDI) Focal Score
A trained assessor interviewed the patient and graded the degree of impairment due to dyspnea (difficulty breathing). TDI focal score is based on three domains: functional impairment, magnitude of task and magnitude of effort and captures changes from baseline. TDI captures changes from baseline, each domain is scored from -3=major deterioration to 3=major improvement to give an overall TDI focal score of -9 to 9. Higher numbers indicate a better score.
Time frame: Week 12
Population: The full analysis set (FAS) consisted of all randomized patients who received at least one dose of study treatment and have at least one evaluable post-baseline assessment.~Following the intent-to-treat principle, patients were analyzed according to the treatment they were assigned to at randomization
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Indacaterol and Glycopyrronium (QVA149) | Baseline Transitional Dyspnea Index (TDI) Focal Score | 0.77 Score | Standard Deviation 1.735 |
| Tiotropium | Baseline Transitional Dyspnea Index (TDI) Focal Score | 0.61 Score | Standard Deviation 1.534 |
p-value: 0.076795% CI: [-0.033, 0.646]ANCOVA
Secondary
Daily Rescue Medication Use (Number of Puffs)
The total number of puffs of rescue medication used over the last 24 hours will be recorded in the patient diary in the morning. The total number of puffs of rescue medication per day over the full 12 weeks will be calculated and divided by the total number of days with non-missing rescue medication data to derive the mean daily number of puffs of rescue medication taken for the patient. The mean daily number of puffs of rescue medication used over 12 weeks will be summarized by treatments
Time frame: Week 12
Population: The full analysis set (FAS) consisted of all randomized patients who received at least one dose of study treatment and have at least one evaluable post-baseline assessment.~Following the intent-to-treat principle, patients were analyzed according to the treatment they were assigned to at randomization
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Indacaterol and Glycopyrronium (QVA149) | Daily Rescue Medication Use (Number of Puffs) | 1.7 Puffs/day | Standard Deviation 0.92 |
| Tiotropium | Daily Rescue Medication Use (Number of Puffs) | 1.8 Puffs/day | Standard Deviation 1.28 |
Secondary
Number of Participants With Change From Baseline on Total Score of COPD Assessment Test (CAT)
Total score of COPD Assessment Test (CAT) will be measured at week 12. This questionnaire is completed by the patient. The score ranges from 0-40 where higher scores represent worse health status. Mild: Score = 0 - 10, Moderate: Score = 11 - 20, Severe: Score = 21 - 30, Very Severe: Score = 31 - 40. The CAT total score was the sum of 8 item scores (each ranging from 0 to 5). If 1 or 2 items were missing, they were replaced with the mean of the completed items. If 3 or more items were missing, the CAT total score was set missing
Time frame: Week 12
Population: The full analysis set (FAS) consisted of all randomized patients who received at least one dose of study treatment and have at least one evaluable post-baseline assessment.~Following the intent-to-treat principle, patients were analyzed according to the treatment they were assigned to at randomization
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Indacaterol and Glycopyrronium (QVA149) | Number of Participants With Change From Baseline on Total Score of COPD Assessment Test (CAT) | Moderate | 92 Number of participants |
| Indacaterol and Glycopyrronium (QVA149) | Number of Participants With Change From Baseline on Total Score of COPD Assessment Test (CAT) | Very severe | 0 Number of participants |
| Indacaterol and Glycopyrronium (QVA149) | Number of Participants With Change From Baseline on Total Score of COPD Assessment Test (CAT) | Severe | 15 Number of participants |
| Indacaterol and Glycopyrronium (QVA149) | Number of Participants With Change From Baseline on Total Score of COPD Assessment Test (CAT) | Missing | 8 Number of participants |
| Indacaterol and Glycopyrronium (QVA149) | Number of Participants With Change From Baseline on Total Score of COPD Assessment Test (CAT) | Mild | 62 Number of participants |
| Tiotropium | Number of Participants With Change From Baseline on Total Score of COPD Assessment Test (CAT) | Missing | 6 Number of participants |
| Tiotropium | Number of Participants With Change From Baseline on Total Score of COPD Assessment Test (CAT) | Mild | 54 Number of participants |
| Tiotropium | Number of Participants With Change From Baseline on Total Score of COPD Assessment Test (CAT) | Moderate | 101 Number of participants |
| Tiotropium | Number of Participants With Change From Baseline on Total Score of COPD Assessment Test (CAT) | Severe | 22 Number of participants |
| Tiotropium | Number of Participants With Change From Baseline on Total Score of COPD Assessment Test (CAT) | Very severe | 1 Number of participants |
p-value: 0.100895% CI: [-1.77, 0.16]ANCOVA
Secondary
Trough Forced Expiratory Volume In One Second (FEV1) After 4 Weeks of Treatment
Spirometry was performed according to internationally accepted standards. Trough FEV1 was defined as the mean of 45 minute and 15 minute pre-dose values.
Time frame: mean of 45 min and 15 min pre-dose week 4
Population: The full analysis set (FAS) consisted of all randomized patients who received at least one dose of study treatment and have at least one evaluable post-baseline assessment.~Following the intent-to-treat principle, patients were analyzed according to the treatment they were assigned to at randomization
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Indacaterol and Glycopyrronium (QVA149) | Trough Forced Expiratory Volume In One Second (FEV1) After 4 Weeks of Treatment | -45min | 0.087 Liters | Standard Deviation 0.2386 |
| Indacaterol and Glycopyrronium (QVA149) | Trough Forced Expiratory Volume In One Second (FEV1) After 4 Weeks of Treatment | -15min | 0.077 Liters | Standard Deviation 0.2298 |
| Tiotropium | Trough Forced Expiratory Volume In One Second (FEV1) After 4 Weeks of Treatment | -15min | 0.024 Liters | Standard Deviation 0.1567 |
| Tiotropium | Trough Forced Expiratory Volume In One Second (FEV1) After 4 Weeks of Treatment | -45min | 0.026 Liters | Standard Deviation 0.1626 |
Comparison: -45 minp-value: 0.005895% CI: [0.017, 0.098]ANCOVA
Comparison: -15minp-value: 0.016195% CI: [0.009, 0.091]ANCOVA