Trial Outcomes & Findings for A Randomized, Multicenter, Open-label, Parallel-group, 12-week Study to Assess the Efficacy and Safety of Switching From Tiotropium to QVA149 (Indacaterol Maleate/Glycopyrronium Bromide) in Symptomatic Mild to Moderate COPD Patients (NCT NCT02566031)
NCT ID: NCT02566031
Last Updated: 2019-09-23
Results Overview
Spirometry was performed according to internationally accepted standards. Trough FEV1 is defined as the mean of 45 minute and 15 minute pre-dose values.
COMPLETED
PHASE4
379 participants
Week 12
2019-09-23
Participant Flow
Participant milestones
| Measure |
Indacaterol and Glycopyrronium (QVA149)
QVA149 110/50 μg capsules for inhalation delivered once daily via single-dose dry powder inhaler (SDPPI) for 12 weeks
|
Tiotropium
Tiotropium 18 μg capsules for inhalation delivered once daily via HandiHaler® device for 12 weeks
|
|---|---|---|
|
Overall Study
STARTED
|
189
|
190
|
|
Overall Study
COMPLETED
|
169
|
178
|
|
Overall Study
NOT COMPLETED
|
20
|
12
|
Reasons for withdrawal
| Measure |
Indacaterol and Glycopyrronium (QVA149)
QVA149 110/50 μg capsules for inhalation delivered once daily via single-dose dry powder inhaler (SDPPI) for 12 weeks
|
Tiotropium
Tiotropium 18 μg capsules for inhalation delivered once daily via HandiHaler® device for 12 weeks
|
|---|---|---|
|
Overall Study
Patient/guardian decision
|
14
|
7
|
|
Overall Study
Protocol deviation
|
2
|
3
|
|
Overall Study
Adverse Event
|
3
|
1
|
|
Overall Study
Lost to Follow-up
|
1
|
1
|
Baseline Characteristics
A Randomized, Multicenter, Open-label, Parallel-group, 12-week Study to Assess the Efficacy and Safety of Switching From Tiotropium to QVA149 (Indacaterol Maleate/Glycopyrronium Bromide) in Symptomatic Mild to Moderate COPD Patients
Baseline characteristics by cohort
| Measure |
Indacaterol and Glycopyrronium (QVA149)
n=189 Participants
QVA149 110/50 μg capsules for inhalation delivered once daily via single-dose dry powder inhaler (SDPPI) for 12 weeks
|
Tiotropium
n=190 Participants
Tiotropium 18 μg capsules for inhalation delivered once daily via HandiHaler® device for 12 weeks
|
Total
n=379 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
69.2 Years
STANDARD_DEVIATION 8.08 • n=5 Participants
|
69.0 Years
STANDARD_DEVIATION 7.54 • n=7 Participants
|
69.1 Years
STANDARD_DEVIATION 7.81 • n=5 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
186 Participants
n=5 Participants
|
183 Participants
n=7 Participants
|
369 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
189 Participants
n=5 Participants
|
190 Participants
n=7 Participants
|
379 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Week 12Population: 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
Spirometry was performed according to internationally accepted standards. Trough FEV1 is defined as the mean of 45 minute and 15 minute pre-dose values.
Outcome measures
| Measure |
Indacaterol and Glycopyrronium (QVA149)
n=177 Participants
QVA149 110/50 μg capsules for inhalation delivered once daily via single-dose dry powder inhaler (SDPPI) for 12 weeks
|
Tiotropium
n=184 Participants
Tiotropium 18 μg capsules for inhalation delivered once daily via HandiHaler® device for 12 weeks
|
|---|---|---|
|
Trough Forced Expiratory Volume In One Second (FEV1) After 12 Weeks of Treatment
|
0.0668 Liters
Standard Deviation 0.18097
|
0.0090 Liters
Standard Deviation 0.18487
|
SECONDARY outcome
Timeframe: mean of 45 min and 15 min pre-dose week 4Population: 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
Spirometry was performed according to internationally accepted standards. Trough FEV1 was defined as the mean of 45 minute and 15 minute pre-dose values.
Outcome measures
| Measure |
Indacaterol and Glycopyrronium (QVA149)
n=177 Participants
QVA149 110/50 μg capsules for inhalation delivered once daily via single-dose dry powder inhaler (SDPPI) for 12 weeks
|
Tiotropium
n=184 Participants
Tiotropium 18 μg capsules for inhalation delivered once daily via HandiHaler® device for 12 weeks
|
|---|---|---|
|
Trough Forced Expiratory Volume In One Second (FEV1) After 4 Weeks of Treatment
-45min
|
0.087 Liters
Standard Deviation 0.2386
|
0.026 Liters
Standard Deviation 0.1626
|
|
Trough Forced Expiratory Volume In One Second (FEV1) After 4 Weeks of Treatment
-15min
|
0.077 Liters
Standard Deviation 0.2298
|
0.024 Liters
Standard Deviation 0.1567
|
SECONDARY outcome
Timeframe: Week 12Population: 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
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.
Outcome measures
| Measure |
Indacaterol and Glycopyrronium (QVA149)
n=177 Participants
QVA149 110/50 μg capsules for inhalation delivered once daily via single-dose dry powder inhaler (SDPPI) for 12 weeks
|
Tiotropium
n=184 Participants
Tiotropium 18 μg capsules for inhalation delivered once daily via HandiHaler® device for 12 weeks
|
|---|---|---|
|
Baseline Transitional Dyspnea Index (TDI) Focal Score
|
0.77 Score
Standard Deviation 1.735
|
0.61 Score
Standard Deviation 1.534
|
SECONDARY outcome
Timeframe: Week 12Population: 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
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
Outcome measures
| Measure |
Indacaterol and Glycopyrronium (QVA149)
n=177 Participants
QVA149 110/50 μg capsules for inhalation delivered once daily via single-dose dry powder inhaler (SDPPI) for 12 weeks
|
Tiotropium
n=184 Participants
Tiotropium 18 μg capsules for inhalation delivered once daily via HandiHaler® device for 12 weeks
|
|---|---|---|
|
Number of Participants With Change From Baseline on Total Score of COPD Assessment Test (CAT)
Mild
|
62 Number of participants
|
54 Number of participants
|
|
Number of Participants With Change From Baseline on Total Score of COPD Assessment Test (CAT)
Moderate
|
92 Number of participants
|
101 Number of participants
|
|
Number of Participants With Change From Baseline on Total Score of COPD Assessment Test (CAT)
Severe
|
15 Number of participants
|
22 Number of participants
|
|
Number of Participants With Change From Baseline on Total Score of COPD Assessment Test (CAT)
Very severe
|
0 Number of participants
|
1 Number of participants
|
|
Number of Participants With Change From Baseline on Total Score of COPD Assessment Test (CAT)
Missing
|
8 Number of participants
|
6 Number of participants
|
SECONDARY outcome
Timeframe: Week 12Population: 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
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
Outcome measures
| Measure |
Indacaterol and Glycopyrronium (QVA149)
n=177 Participants
QVA149 110/50 μg capsules for inhalation delivered once daily via single-dose dry powder inhaler (SDPPI) for 12 weeks
|
Tiotropium
n=184 Participants
Tiotropium 18 μg capsules for inhalation delivered once daily via HandiHaler® device for 12 weeks
|
|---|---|---|
|
Daily Rescue Medication Use (Number of Puffs)
|
1.7 Puffs/day
Standard Deviation 0.92
|
1.8 Puffs/day
Standard Deviation 1.28
|
Adverse Events
Indacaterol and Glycopyrronium (QVA149
Tiotropium
Total
Serious adverse events
| Measure |
Indacaterol and Glycopyrronium (QVA149
n=189 participants at risk
QVA149 110/50 μg capsules for inhalation delivered once daily via single-dose dry powder inhaler (SDPPI) for 12 weeks
|
Tiotropium
n=188 participants at risk
Tiotropium 18 μg capsules for inhalation delivered once daily via HandiHaler® device for 12 weeks
|
Total
n=377 participants at risk
Total
|
|---|---|---|---|
|
Cardiac disorders
Angina pectoris
|
0.53%
1/189 • 12 Weeks
|
0.00%
0/188 • 12 Weeks
|
0.27%
1/377 • 12 Weeks
|
|
Infections and infestations
Pneumonia
|
1.1%
2/189 • 12 Weeks
|
0.00%
0/188 • 12 Weeks
|
0.53%
2/377 • 12 Weeks
|
|
Injury, poisoning and procedural complications
Femoral neck fracture
|
0.53%
1/189 • 12 Weeks
|
0.00%
0/188 • 12 Weeks
|
0.27%
1/377 • 12 Weeks
|
|
Injury, poisoning and procedural complications
Fracture
|
0.00%
0/189 • 12 Weeks
|
0.53%
1/188 • 12 Weeks
|
0.27%
1/377 • 12 Weeks
|
|
Injury, poisoning and procedural complications
Rib fracture
|
0.00%
0/189 • 12 Weeks
|
0.53%
1/188 • 12 Weeks
|
0.27%
1/377 • 12 Weeks
|
|
Nervous system disorders
Carotid artery stenosis
|
0.53%
1/189 • 12 Weeks
|
0.00%
0/188 • 12 Weeks
|
0.27%
1/377 • 12 Weeks
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
1.6%
3/189 • 12 Weeks
|
0.53%
1/188 • 12 Weeks
|
1.1%
4/377 • 12 Weeks
|
Other adverse events
| Measure |
Indacaterol and Glycopyrronium (QVA149
n=189 participants at risk
QVA149 110/50 μg capsules for inhalation delivered once daily via single-dose dry powder inhaler (SDPPI) for 12 weeks
|
Tiotropium
n=188 participants at risk
Tiotropium 18 μg capsules for inhalation delivered once daily via HandiHaler® device for 12 weeks
|
Total
n=377 participants at risk
Total
|
|---|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
6.3%
12/189 • 12 Weeks
|
4.8%
9/188 • 12 Weeks
|
5.6%
21/377 • 12 Weeks
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety
- Publication restrictions are in place
Restriction type: OTHER