Trial Outcomes & Findings for Randomized, Double-blind, Placebo-controlled, Multicenter, Cross-over Study to Assess the Effects of a 3 Week Therapy Each With QVA149 Versus Placebo on Pulmonary Function and Average Physical Activity Levels in Patients With COPD. (NCT NCT01996319)
NCT ID: NCT01996319
Last Updated: 2016-04-05
Results Overview
Inspiratory capacity (IC) will be measured with spirometry conducted according to internationally accepted standards. The mean of 3 acceptable measurements will be calculated and reported in liters. In this cross-over trial, we had two baselines collected at day 1 and collected at day 36. From the IC measurements collected on either Day 22 or 57, respectively, the appropriate baseline measurements were subtracted - so either Day 22-Day1 or Day 57-Day36
COMPLETED
PHASE3
194 participants
Baseline, day 22, baseline day 36, day 57
2016-04-05
Participant Flow
Participant milestones
| Measure |
QVA149 Then Placebo
QVA149 once a day during 22 days cross-over to placebo once a day for up to 22 days
|
Placebo Then QVA149
Placebo once a day during 22 days cross-over to QVA149 once a day for 22 days
|
|---|---|---|
|
Overall Study
STARTED
|
96
|
98
|
|
Overall Study
COMPLETED
|
88
|
95
|
|
Overall Study
NOT COMPLETED
|
8
|
3
|
Reasons for withdrawal
| Measure |
QVA149 Then Placebo
QVA149 once a day during 22 days cross-over to placebo once a day for up to 22 days
|
Placebo Then QVA149
Placebo once a day during 22 days cross-over to QVA149 once a day for 22 days
|
|---|---|---|
|
Overall Study
Protocol Violation
|
1
|
0
|
|
Overall Study
Severe or moderate (COPD) Exacerbation
|
5
|
1
|
|
Overall Study
Adverse Event
|
2
|
2
|
Baseline Characteristics
Randomized, Double-blind, Placebo-controlled, Multicenter, Cross-over Study to Assess the Effects of a 3 Week Therapy Each With QVA149 Versus Placebo on Pulmonary Function and Average Physical Activity Levels in Patients With COPD.
Baseline characteristics by cohort
| Measure |
QVA149 Then Placebo
n=96 Participants
QVA149 once a day during 22 days cross-over to placebo once a day for up to 22 days
|
Placebo Then QVA149
n=98 Participants
Placebo once a day during 22 days cross-over to QVA149 once a day for 22 days
|
Total
n=194 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
64.3 Years
STANDARD_DEVIATION 7.9 • n=39 Participants
|
61.2 Years
STANDARD_DEVIATION 7.7 • n=41 Participants
|
62.8 Years
STANDARD_DEVIATION 7.9 • n=35 Participants
|
|
Sex: Female, Male
Female
|
32 Participants
n=39 Participants
|
35 Participants
n=41 Participants
|
67 Participants
n=35 Participants
|
|
Sex: Female, Male
Male
|
64 Participants
n=39 Participants
|
63 Participants
n=41 Participants
|
127 Participants
n=35 Participants
|
PRIMARY outcome
Timeframe: Baseline, day 22, baseline day 36, day 57Population: Full Analysis Set (FAS): all randomized patients who applied at least one dose of study medication during at least one study period. all patients were included in these analyses when baseline and day 22 data plus baseline day 36 and day 57 data were available.
Inspiratory capacity (IC) will be measured with spirometry conducted according to internationally accepted standards. The mean of 3 acceptable measurements will be calculated and reported in liters. In this cross-over trial, we had two baselines collected at day 1 and collected at day 36. From the IC measurements collected on either Day 22 or 57, respectively, the appropriate baseline measurements were subtracted - so either Day 22-Day1 or Day 57-Day36
Outcome measures
| Measure |
QVA149
n=189 Participants
|
Placebo
n=184 Participants
|
|---|---|---|
|
Change From Baseline in Peak Inspiratory Capacity (IC) Comparison Between QVA149 and Placebo
|
0.3790 Liters
95% Confidence Interval 0.2747 • Interval 0.3464 to 0.4117
|
0.1769 Liters
95% Confidence Interval 0.1933 • Interval 0.1379 to 0.2159
|
PRIMARY outcome
Timeframe: Baseline, day 22, baseline day 36, day 57Population: Full Analysis Set (FAS): all randomized patients who applied at least one dose of study medication during at least one study period. Only patients with baseline and day 22 data, plus baseline on day 36 and day 57 data were included in this analysis.
Average physical activity level is defined by average daily activity-related energy consumption \[Kcal/day\], measured via Actinography device. In this cross-over trial, we had two baselines collected at day 1 and collected at day 36. From the activity measurements collected on either Day 22 or 57, respectively, the appropriate baseline measurements were subtracted - so either Day 22-Day1 or Day 57-Day36
Outcome measures
| Measure |
QVA149
n=175 Participants
|
Placebo
n=170 Participants
|
|---|---|---|
|
Change From Baseline in the Comparison of QVA149 Versus Placebo With Respect to Average Physical Activity Level
|
5.1063 kcal/day
95% Confidence Interval 214.6 • Interval -24.4 to 34.6125
|
-31.6063 kcal/day
95% Confidence Interval 233.0 • Interval -61.5268 to -1.6857
|
SECONDARY outcome
Timeframe: Baseline, day 22, baseline day 36, day 57Population: Full Analysis Set (FAS): all randomized patients who applied at least one dose of study medication during at least one study period. Only patients with baseline and day 22 data, plus baseline on day 36 and day 57 data were included in this analysis
The average number of steps per day will be measured via Actinography device. In this cross-over trial, we had two baselines collected at day 1 and collected at day 36. From the activity measurements collected on either Day 22 or 57, respectively, the appropriate baseline measurements were subtracted - so either Day 22-Day 1 or Day 57-Day36
Outcome measures
| Measure |
QVA149
n=178 Participants
|
Placebo
n=173 Participants
|
|---|---|---|
|
Change in the Comparison of QVA149 vs. Placebo on the Average Number of Steps Per Day
|
30.7 Steps/day
Standard Deviation 1662
|
-320.7 Steps/day
Standard Deviation 1648
|
SECONDARY outcome
Timeframe: Baseline, day 22, baseline day 36, day 57Population: Full Analysis Set (FAS): all randomized patients who applied at least one dose of study medication during at least one study period. Only patients with baseline and day 22, plus baseline day 36 and day 57 data were included in this analysis.
Least moderate activity (defined as 3,5-7kcal/min) will be measured via Actinography device. In this cross-over trial, we had two baselines collected at day 1 and collected at day 36. From the activity measurements collected on either Day 22 or 57, respectively, the appropriate baseline measurements were subtracted - so either Day 22-Day1 or Day 57-Day36
Outcome measures
| Measure |
QVA149
n=178 Participants
|
Placebo
n=173 Participants
|
|---|---|---|
|
Change in the Duration of at Least Moderate Activity Per Day Comparison of QVA149 Versus Placebo
|
-5.5 Minutes
Standard Deviation 51.8
|
-13.0 Minutes
Standard Deviation 52.3
|
SECONDARY outcome
Timeframe: Day 1 or day 36Population: Full Analysis Set (FAS): all randomized patients who applied at least one dose of study medication during at least one study period. Only patients with baseline and day 1 post treatment initiation were included in this analysis.
Inspiratory capacity (IC) will be measured with spirometry conducted according to internationally accepted standards. The mean of 3 acceptable measurements will be calculated and reported in liters. In this cross-over trial, we had two baselines collected at day 1 and collected at day 36. The IC measurements collected prior to dosing on either Day 1 or 36, respectively, were subtracted from the appropriate peak measures on the same respective days
Outcome measures
| Measure |
QVA149
n=193 Participants
|
Placebo
n=186 Participants
|
|---|---|---|
|
Change From Baseline in Peak IC Comparison Between QVA149 and Placebo on Day 1.
|
0.486 Liters
Standard Deviation 0.2752
|
0.207 Liters
Standard Deviation 0.2114
|
SECONDARY outcome
Timeframe: Baseline, day 22, baseline day 36, day 57Population: Full Analysis Set (FAS): all randomized patients who applied at least one dose of study medication during at least one study period. Only patients with baseline and day 20 post treatment initiation were included in this analysis.
Inspiratory capacity (IC) will be measured with spirometry conducted according to internationally accepted standards. The mean of 3 acceptable measurements will be calculated and reported in liters. In this cross-over trial, we had two baselines collected at day 1 and collected at day 36. From the IC measurements collected on either Day 22 or 57, respectively, the appropriate baseline measurements were subtracted - so either Day 22-Day1 or Day 57-Day36
Outcome measures
| Measure |
QVA149
n=190 Participants
|
Placebo
n=183 Participants
|
|---|---|---|
|
Change From Baseline in the Trough IC Comparison Between QVA149 and Placebo
|
0.210 Liters
Standard Deviation 0.346
|
-0.035 Liters
Standard Deviation 0.279
|
SECONDARY outcome
Timeframe: Day 1 or day 36Population: Full Analysis Set (FAS): all randomized patients who applied at least one dose of study medication during at least one study period
FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation, measured through spirometry testing. The mean of 3 acceptable measurements will be calculated and reported in liters. In this cross-over trial, we had two baselines collected at day 1 and collected at day 36. The FEV1 measurements collected prior to dosing on either Day 1 or 36, respectively, were subtracted from the appropriate peak measures on the same respective days
Outcome measures
| Measure |
QVA149
n=192 Participants
|
Placebo
n=186 Participants
|
|---|---|---|
|
Peak Forced Expiratory Volume 1 (FEV1) Comparison Between QVA149 and Placebo at Day 1
|
0.347 Liters
Standard Deviation 0.176
|
0.111 Liters
Standard Deviation 0.179
|
SECONDARY outcome
Timeframe: Baseline, day 22, baseline day 36, day 57Population: Full Analysis Set (FAS): all randomized patients who applied at least one dose of study medication during at least one study period
FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation, measured through spirometry testing. The mean of 3 acceptable measurements will be calculated and reported in liters. In this cross-over trial, we had two baselines collected at day 1 and collected at day 36. From the FEV1 measurements collected on either Day 22 or 57, respectively, the appropriate baseline measurements were subtracted - so either Day 22-Day1 or Day 57-Day36
Outcome measures
| Measure |
QVA149
n=188 Participants
|
Placebo
n=183 Participants
|
|---|---|---|
|
Trough FEV1 Comparison Between QVA149 and Placebo After 22 Days
|
0.245 Liters
Standard Deviation 0.221
|
-0.058 Liters
Standard Deviation 0.207
|
Adverse Events
QVA149 Then Placebo
Placebo Then QVA149
Serious adverse events
| Measure |
QVA149 Then Placebo
n=193 participants at risk
QVA149 once a day during 22 days cross-over to placebo once a day for up to 22 days
|
Placebo Then QVA149
n=188 participants at risk
Placebo once a day during 22 days cross-over to QVA149 once a day for 22 days
|
|---|---|---|
|
Cardiac disorders
Myocardial infarction
|
0.52%
1/193
|
0.00%
0/188
|
|
Infections and infestations
Cellulitis
|
0.52%
1/193
|
0.00%
0/188
|
|
Injury, poisoning and procedural complications
Incisional hernia
|
0.52%
1/193
|
0.53%
1/188
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bone cancer
|
0.52%
1/193
|
0.00%
0/188
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Oesophageal carcinoma
|
0.00%
0/193
|
0.53%
1/188
|
Other adverse events
| Measure |
QVA149 Then Placebo
n=193 participants at risk
QVA149 once a day during 22 days cross-over to placebo once a day for up to 22 days
|
Placebo Then QVA149
n=188 participants at risk
Placebo once a day during 22 days cross-over to QVA149 once a day for 22 days
|
|---|---|---|
|
General disorders
Fatigue
|
1.0%
2/193
|
0.00%
0/188
|
|
Infections and infestations
Nasopharyngitis
|
3.6%
7/193
|
4.3%
8/188
|
|
Infections and infestations
Rhinitis
|
1.0%
2/193
|
1.1%
2/188
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
1.6%
3/193
|
1.6%
3/188
|
|
Nervous system disorders
Headache
|
3.1%
6/193
|
1.6%
3/188
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
4.1%
8/193
|
1.6%
3/188
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
1.0%
2/193
|
0.53%
1/188
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
1.0%
2/193
|
0.00%
0/188
|
|
Respiratory, thoracic and mediastinal disorders
Sputum increased
|
1.6%
3/193
|
0.00%
0/188
|
Additional Information
Study Director
Novartis Pharmaceuticals
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