Trial Outcomes & Findings for Pharmacodynamics, Safety, Tolerability, and Pharmacokinetics of Two Orally Inhaled Indacaterol Salts in Adult Subjects With Asthma. (NCT NCT03257995)
NCT ID: NCT03257995
Last Updated: 2021-01-05
Results Overview
FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of forced exhalation. Treatment differences in trough FEV1 after 14 days of treatment between indacaterol maleate 150 μg and placebo, between indacaterol acetate 150 μg and placebo and indacaterol maleate and indacaterol acetate
COMPLETED
PHASE2
54 participants
Day 14 of each of the three treatment periods
2021-01-05
Participant Flow
Participant milestones
| Measure |
Sequence 1
indacaterol maleate 150 μg , indacaterol acetate 150 μg and matching placebo
|
Sequence 2
indacaterol acetate 150 μg, matching placebo and indacaterol maleate 150 μg
|
Sequence 3
Placebo, indacaterol maleate 150 μg and indacaterol acetate 150 μg
|
Sequence 4
indacaterol maleate 150 μg, placebo, and indacaterol acetate 150 μg
|
Sequence 5
indacaterol acetate 150 μg, indacaterol maleate 150 μg, and placebo
|
Sequence 6
Placebo, indacaterol acetate 150 μg, indacaterol maleate 150 μg
|
|---|---|---|---|---|---|---|
|
Overall Study
STARTED
|
9
|
9
|
9
|
9
|
9
|
9
|
|
Overall Study
COMPLETED
|
9
|
8
|
9
|
9
|
9
|
7
|
|
Overall Study
NOT COMPLETED
|
0
|
1
|
0
|
0
|
0
|
2
|
Reasons for withdrawal
| Measure |
Sequence 1
indacaterol maleate 150 μg , indacaterol acetate 150 μg and matching placebo
|
Sequence 2
indacaterol acetate 150 μg, matching placebo and indacaterol maleate 150 μg
|
Sequence 3
Placebo, indacaterol maleate 150 μg and indacaterol acetate 150 μg
|
Sequence 4
indacaterol maleate 150 μg, placebo, and indacaterol acetate 150 μg
|
Sequence 5
indacaterol acetate 150 μg, indacaterol maleate 150 μg, and placebo
|
Sequence 6
Placebo, indacaterol acetate 150 μg, indacaterol maleate 150 μg
|
|---|---|---|---|---|---|---|
|
Overall Study
Adverse Event
|
0
|
1
|
0
|
0
|
0
|
0
|
|
Overall Study
Protocol deviation
|
0
|
0
|
0
|
0
|
0
|
2
|
Baseline Characteristics
Pharmacodynamics, Safety, Tolerability, and Pharmacokinetics of Two Orally Inhaled Indacaterol Salts in Adult Subjects With Asthma.
Baseline characteristics by cohort
| Measure |
All Participants
n=54 Participants
All participants randomized to one of six treatment sequences
|
|---|---|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
7 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
47 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Age, Continuous
|
47.7 years
STANDARD_DEVIATION 12.5 • n=5 Participants
|
|
Sex: Female, Male
Female
|
36 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
18 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Day 14 of each of the three treatment periodsPopulation: The PD analysis set included all patients with available PD parameter data who received any study drug and experienced no major protocol deviations with relevant impact on PD data
FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of forced exhalation. Treatment differences in trough FEV1 after 14 days of treatment between indacaterol maleate 150 μg and placebo, between indacaterol acetate 150 μg and placebo and indacaterol maleate and indacaterol acetate
Outcome measures
| Measure |
Indacaterol Maleate
n=51 Participants
indacaterol maleate 150 μg via Breezhaler
|
Indacaterol Acetate
n=52 Participants
indacaterol acetate 150 μg via Breezhaler
|
Placebo
n=53 Participants
matching placebo capsules to indacaterol via Breezhaler
|
|---|---|---|---|
|
Trough FEV1
|
2.4173 Liters
Standard Deviation 0.78214
|
2.3774 Liters
Standard Deviation 0.77679
|
2.2191 Liters
Standard Deviation 0.72350
|
SECONDARY outcome
Timeframe: Day 14 of each of the three treatment periodsPopulation: The PK analysis set included all patients with at least one available valid (i.e. not flagged for exclusion) PK concentration measurement, who received any study drug and experienced no major protocol deviations with relevant impact on PK data.
AUC 0-24hours of plasma concentrations of indacaterol maleate and indacaterol acetate at steady state.The area under the concentrations-time curve (AUC0-24) was calculated with the measured data points from the time of administration up to 24 h after administration by the trapezoidal formula. The concentration-time curve is the result of time points of blood sampling and its measured concentration in the blood samplings
Outcome measures
| Measure |
Indacaterol Maleate
n=51 Participants
indacaterol maleate 150 μg via Breezhaler
|
Indacaterol Acetate
n=52 Participants
indacaterol acetate 150 μg via Breezhaler
|
Placebo
matching placebo capsules to indacaterol via Breezhaler
|
|---|---|---|---|
|
Pharmacokinetics AUC 0-24hours at Steady State
|
2300 h*pg/mL
Standard Deviation 732
|
2050 h*pg/mL
Standard Deviation 636
|
—
|
SECONDARY outcome
Timeframe: Day 14 of each of the three treatment periodsPopulation: The PK analysis set included all patients with at least one available valid (i.e. not flagged for exclusion) PK concentration measurement, who received any study drug and experienced no major protocol deviations with relevant impact on PK data.
Maximal plasma concentrations of indacaterol maleate and indacaterol acetate at steady state. The maximum concentration (Cmax) were obtained directly from the measured concentration-time curves. The concentration-time curve is the result of time points of blood sampling and its measured concentration in the blood samplings.
Outcome measures
| Measure |
Indacaterol Maleate
n=51 Participants
indacaterol maleate 150 μg via Breezhaler
|
Indacaterol Acetate
n=52 Participants
indacaterol acetate 150 μg via Breezhaler
|
Placebo
matching placebo capsules to indacaterol via Breezhaler
|
|---|---|---|---|
|
The Maximum Concentration (Cmax) at Steady State (ss)
|
249 pg/mL
Interval 126.0 to 443.0
|
224 pg/mL
Interval 84.9 to 426.0
|
—
|
SECONDARY outcome
Timeframe: Day 14 of each of the three treatment periodsPopulation: The PK analysis set included all patients with at least one available valid (i.e. not flagged for exclusion) PK concentration measurement, who received any study drug and experienced no major protocol deviations with relevant impact on PK data.
Time of maximal plasma concentration of indacaterol maleate and indacaterol acetate at steady state. Time to reach the maximum concentration after administration. In this analysis Tmax will be reported using blood samples taken on Days 14
Outcome measures
| Measure |
Indacaterol Maleate
n=51 Participants
indacaterol maleate 150 μg via Breezhaler
|
Indacaterol Acetate
n=52 Participants
indacaterol acetate 150 μg via Breezhaler
|
Placebo
matching placebo capsules to indacaterol via Breezhaler
|
|---|---|---|---|
|
Time of Maximal Plasma Concentration (Tmax) at Steady State
|
0.250 h
Interval 0.183 to 0.85
|
0.467 h
Interval 0.183 to 1.0
|
—
|
SECONDARY outcome
Timeframe: Day 14 of each of the three treatment periodsPopulation: The PK analysis set included all patients with at least one available valid (i.e. not flagged for exclusion) PK concentration measurement, who received any study drug and experienced no major protocol deviations with relevant impact on PK data.
The lowest plasma (or serum or blood) concentration observed during a dosing interval at steady state. Only summary statistics was provided.
Outcome measures
| Measure |
Indacaterol Maleate
n=51 Participants
indacaterol maleate 150 μg via Breezhaler
|
Indacaterol Acetate
n=52 Participants
indacaterol acetate 150 μg via Breezhaler
|
Placebo
matching placebo capsules to indacaterol via Breezhaler
|
|---|---|---|---|
|
The Lowest Plasma (or Serum or Blood) Concentration (Cmin) at Steady State
|
56 pg/mL
Interval 14.5 to 126.0
|
52.3 pg/mL
Interval 9.03 to 106.0
|
—
|
SECONDARY outcome
Timeframe: Day 14Population: The PK analysis set included all patients with at least one available valid (i.e. not flagged for exclusion) PK concentration measurement, who received any study drug and experienced no major protocol deviations with relevant impact on PK data. Only summary statistics for relative bioavailability was provided.
Relative bioavailability will be determined for AUC0-24h,ss and Cmax,ss comparing systemic exposure of indacaterol acetate and indacaterol maleate.
Outcome measures
| Measure |
Indacaterol Maleate
n=43 Participants
indacaterol maleate 150 μg via Breezhaler
|
Indacaterol Acetate
n=45 Participants
indacaterol acetate 150 μg via Breezhaler
|
Placebo
matching placebo capsules to indacaterol via Breezhaler
|
|---|---|---|---|
|
Relative Bioavailability (Frel) of Indacaterol Acetate and Indacaterol Maleate
|
0.912 Ratio
Standard Deviation 0.201
|
0.910 Ratio
Standard Deviation 0.242
|
—
|
SECONDARY outcome
Timeframe: Day 14 of each of the three treatment periodsPopulation: The PD analysis set included all patients with available PD parameter data who received any study drug and experienced no major protocol deviations with relevant impact on PD data
The differences in median time to peak FEV1 (h) between indacaterol maleate 150 µg and placebo
Outcome measures
| Measure |
Indacaterol Maleate
n=51 Participants
indacaterol maleate 150 μg via Breezhaler
|
Indacaterol Acetate
n=51 Participants
indacaterol acetate 150 μg via Breezhaler
|
Placebo
n=51 Participants
matching placebo capsules to indacaterol via Breezhaler
|
|---|---|---|---|
|
Time to Peak FEV1 on Day 14
|
-0.02 h
Interval -0.83 to 0.33
|
-0.02 h
Interval -0.82 to 0.51
|
0.00 h
Interval -0.5 to 0.73
|
SECONDARY outcome
Timeframe: Day 14 of each of the three treatment periods at 5, 15, 30m, 1 2, 3, 4, 8, 12, 23hour.15min and 23hour.45minPopulation: The PD analysis set included all patients with available PD parameter data who received any study drug and experienced no major protocol deviations with relevant impact on PD data
Bronchodilator effect of indacaterol salts compared to placebo in terms of FEV1. Day 14, FEV1 was measured at 24hours post dose
Outcome measures
| Measure |
Indacaterol Maleate
n=51 Participants
indacaterol maleate 150 μg via Breezhaler
|
Indacaterol Acetate
n=52 Participants
indacaterol acetate 150 μg via Breezhaler
|
Placebo
n=53 Participants
matching placebo capsules to indacaterol via Breezhaler
|
|---|---|---|---|
|
Bronchodilator Effect of Indacaterol Salts Compared to Placebo Measured by Forced Expiratory Volume in 1 Second (FEV1) at All Timepoints
5 min
|
2.4795 Liter
Interval 2.2575 to 2.7014
|
2.4813 Liter
Interval 2.2595 to 2.7031
|
2.2617 Liter
Interval 2.0398 to 2.4837
|
|
Bronchodilator Effect of Indacaterol Salts Compared to Placebo Measured by Forced Expiratory Volume in 1 Second (FEV1) at All Timepoints
15 min
|
2.5005 Liter
Interval 2.2786 to 2.7224
|
2.4965 Liter
Interval 2.2746 to 2.7184
|
2.2282 Liter
Interval 2.0062 to 2.4501
|
|
Bronchodilator Effect of Indacaterol Salts Compared to Placebo Measured by Forced Expiratory Volume in 1 Second (FEV1) at All Timepoints
30 min
|
2.5204 Liter
Interval 2.2985 to 2.7424
|
2.5047 Liter
Interval 2.2829 to 2.7265
|
2.2475 Liter
Interval 2.0255 to 2.4694
|
|
Bronchodilator Effect of Indacaterol Salts Compared to Placebo Measured by Forced Expiratory Volume in 1 Second (FEV1) at All Timepoints
1 hour
|
2.5279 Liter
Interval 2.306 to 2.7498
|
2.5018 Liter
Interval 2.28 to 2.7236
|
2.2670 Liter
Interval 2.0451 to 2.4889
|
|
Bronchodilator Effect of Indacaterol Salts Compared to Placebo Measured by Forced Expiratory Volume in 1 Second (FEV1) at All Timepoints
2 hour
|
2.5286 Liter
Interval 2.3067 to 2.7505
|
2.5338 Liter
Interval 2.312 to 2.7556
|
2.2792 Liter
Interval 2.0573 to 2.5011
|
|
Bronchodilator Effect of Indacaterol Salts Compared to Placebo Measured by Forced Expiratory Volume in 1 Second (FEV1) at All Timepoints
4 hour
|
2.5054 Liter
Interval 2.2835 to 2.7273
|
2.5103 Liter
Interval 2.2885 to 2.7321
|
2.2781 Liter
Interval 2.0561 to 2.5001
|
|
Bronchodilator Effect of Indacaterol Salts Compared to Placebo Measured by Forced Expiratory Volume in 1 Second (FEV1) at All Timepoints
8 hour
|
2.4668 Liter
Interval 2.2448 to 2.6888
|
2.4596 Liter
Interval 2.2378 to 2.6814
|
2.2272 Liter
Interval 2.0052 to 2.4492
|
|
Bronchodilator Effect of Indacaterol Salts Compared to Placebo Measured by Forced Expiratory Volume in 1 Second (FEV1) at All Timepoints
12 hour
|
2.4222 Liter
Interval 2.2002 to 2.6442
|
2.3836 Liter
Interval 2.1618 to 2.6054
|
2.1779 Liter
Interval 1.9558 to 2.3999
|
|
Bronchodilator Effect of Indacaterol Salts Compared to Placebo Measured by Forced Expiratory Volume in 1 Second (FEV1) at All Timepoints
23 hour 15 min
|
2.4678 Liter
Interval 2.2457 to 2.6899
|
2.4022 Liter
Interval 2.1804 to 2.6241
|
2.2398 Liter
Interval 2.0173 to 2.4622
|
|
Bronchodilator Effect of Indacaterol Salts Compared to Placebo Measured by Forced Expiratory Volume in 1 Second (FEV1) at All Timepoints
23 hour 45 min
|
2.4585 Liter
Interval 2.2364 to 2.6806
|
2.4424 Liter
Interval 2.2205 to 2.6642
|
2.2631 Liter
Interval 2.0407 to 2.4856
|
SECONDARY outcome
Timeframe: Day 14 of each of the three treatment periods at 5, 15, 30m, 1 2, 3, 4, 8, 12, 23hour.15min and 23hour.45minPopulation: The PD analysis set included all patients with available PD parameter data who received any study drug and experienced no major protocol deviations with relevant impact on PD data
The FEV1 percent predicted expresses FEV1 as a percentage of the "predicted values" for participants of similar characteristics (height, age, sex, and sometimes race and weight). A positive change from baseline in FEV1 % predicted indicates improvement in lung function. FEV1 % predicted was assessed at each post dose time point after 14 days
Outcome measures
| Measure |
Indacaterol Maleate
n=51 Participants
indacaterol maleate 150 μg via Breezhaler
|
Indacaterol Acetate
n=52 Participants
indacaterol acetate 150 μg via Breezhaler
|
Placebo
n=53 Participants
matching placebo capsules to indacaterol via Breezhaler
|
|---|---|---|---|
|
Percent of Predicted Bronchodilator Effect of Indacaterol Salts Compared to Placebo Measured by FEV1 (% Predicted) at All Timepoints
12 hours
|
76.2 Percent of predicted
Interval 72.7 to 79.7
|
75.0 Percent of predicted
Interval 71.5 to 78.5
|
68.6 Percent of predicted
Interval 65.2 to 72.1
|
|
Percent of Predicted Bronchodilator Effect of Indacaterol Salts Compared to Placebo Measured by FEV1 (% Predicted) at All Timepoints
5 min
|
78.2 Percent of predicted
Interval 74.7 to 81.7
|
78.2 Percent of predicted
Interval 74.8 to 81.7
|
71.1 Percent of predicted
Interval 67.7 to 74.6
|
|
Percent of Predicted Bronchodilator Effect of Indacaterol Salts Compared to Placebo Measured by FEV1 (% Predicted) at All Timepoints
15 min
|
78.7 Percent of predicted
Interval 75.2 to 82.2
|
78.5 Percent of predicted
Interval 75.0 to 82.0
|
70.2 Percent of predicted
Interval 66.7 to 73.7
|
|
Percent of Predicted Bronchodilator Effect of Indacaterol Salts Compared to Placebo Measured by FEV1 (% Predicted) at All Timepoints
30 min
|
79.4 Percent of predicted
Interval 75.9 to 82.9
|
78.9 Percent of predicted
Interval 75.4 to 82.3
|
70.7 Percent of predicted
Interval 67.3 to 74.2
|
|
Percent of Predicted Bronchodilator Effect of Indacaterol Salts Compared to Placebo Measured by FEV1 (% Predicted) at All Timepoints
1 hour
|
79.5 Percent of predicted
Interval 76.0 to 83.0
|
78.8 Percent of predicted
Interval 75.3 to 82.3
|
71.4 Percent of predicted
Interval 67.9 to 74.9
|
|
Percent of Predicted Bronchodilator Effect of Indacaterol Salts Compared to Placebo Measured by FEV1 (% Predicted) at All Timepoints
2 hours
|
79.6 Percent of predicted
Interval 76.1 to 83.1
|
79.8 Percent of predicted
Interval 76.3 to 83.2
|
72.0 Percent of predicted
Interval 68.5 to 75.5
|
|
Percent of Predicted Bronchodilator Effect of Indacaterol Salts Compared to Placebo Measured by FEV1 (% Predicted) at All Timepoints
4 hours
|
78.8 Percent of predicted
Interval 75.4 to 82.3
|
79.1 Percent of predicted
Interval 75.6 to 82.5
|
71.8 Percent of predicted
Interval 68.3 to 75.3
|
|
Percent of Predicted Bronchodilator Effect of Indacaterol Salts Compared to Placebo Measured by FEV1 (% Predicted) at All Timepoints
8 hours
|
77.5 Percent of predicted
Interval 74.0 to 81.0
|
77.5 Percent of predicted
Interval 74.1 to 81.0
|
70.2 Percent of predicted
Interval 66.7 to 73.6
|
|
Percent of Predicted Bronchodilator Effect of Indacaterol Salts Compared to Placebo Measured by FEV1 (% Predicted) at All Timepoints
23 hours 15 min
|
77.9 Percent of predicted
Interval 74.5 to 81.4
|
76.1 Percent of predicted
Interval 72.6 to 79.5
|
71.0 Percent of predicted
Interval 67.5 to 74.5
|
|
Percent of Predicted Bronchodilator Effect of Indacaterol Salts Compared to Placebo Measured by FEV1 (% Predicted) at All Timepoints
23 hours 45 min
|
77.8 Percent of predicted
Interval 74.3 to 81.3
|
77.2 Percent of predicted
Interval 73.7 to 80.7
|
71.4 Percent of predicted
Interval 67.8 to 74.9
|
SECONDARY outcome
Timeframe: Day 14 of each of the three treatment periods at at 5, 15, 30m, 1 2, 3, 4, 8, 12, 23hour.15min and 23hour.45minPopulation: The PD analysis set included all patients with available PD parameter data who received any study drug and experienced no major protocol deviations with relevant impact on PD data
Forced Vital Capacity is the amount of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. FVC was assessed by spirometry at each post dose time point after 14 days. A positive change from baseline in FVC indicates improvement in lung function.
Outcome measures
| Measure |
Indacaterol Maleate
n=51 Participants
indacaterol maleate 150 μg via Breezhaler
|
Indacaterol Acetate
n=52 Participants
indacaterol acetate 150 μg via Breezhaler
|
Placebo
n=53 Participants
matching placebo capsules to indacaterol via Breezhaler
|
|---|---|---|---|
|
Bronchodilator Effect of Indacaterol Salts Compared to Placebo Measured by Forced Vital Capacity (FVC)
5 min
|
3.5648 liter
Interval 3.2407 to 3.889
|
3.5912 liter
Interval 3.2672 to 3.9152
|
3.3783 liter
Interval 3.0541 to 3.7024
|
|
Bronchodilator Effect of Indacaterol Salts Compared to Placebo Measured by Forced Vital Capacity (FVC)
15 min
|
3.5850 liter
Interval 3.2608 to 3.9091
|
3.5773 liter
Interval 3.2531 to 3.9015
|
3.3600 liter
Interval 3.0359 to 3.6842
|
|
Bronchodilator Effect of Indacaterol Salts Compared to Placebo Measured by Forced Vital Capacity (FVC)
4 hour
|
3.5674 liter
Interval 3.2433 to 3.8916
|
3.5999 liter
Interval 3.2759 to 3.924
|
3.4053 liter
Interval 3.0812 to 3.7295
|
|
Bronchodilator Effect of Indacaterol Salts Compared to Placebo Measured by Forced Vital Capacity (FVC)
12 hour
|
3.4941 liter
Interval 3.1698 to 3.8183
|
3.4812 liter
Interval 3.1571 to 3.8053
|
3.3193 liter
Interval 2.995 to 3.6436
|
|
Bronchodilator Effect of Indacaterol Salts Compared to Placebo Measured by Forced Vital Capacity (FVC)
23 hour 45 min
|
3.5668 liter
Interval 3.2425 to 3.8912
|
3.5731 liter
Interval 3.2489 to 3.8972
|
3.4185 liter
Interval 3.0938 to 3.7431
|
|
Bronchodilator Effect of Indacaterol Salts Compared to Placebo Measured by Forced Vital Capacity (FVC)
30 min
|
3.6068 liter
Interval 3.2827 to 3.931
|
3.6039 liter
Interval 3.2798 to 3.9279
|
3.3664 liter
Interval 3.0422 to 3.6905
|
|
Bronchodilator Effect of Indacaterol Salts Compared to Placebo Measured by Forced Vital Capacity (FVC)
1 hour
|
3.5946 liter
Interval 3.2705 to 3.9188
|
3.5886 liter
Interval 3.2645 to 3.9126
|
3.3873 liter
Interval 3.0631 to 3.7114
|
|
Bronchodilator Effect of Indacaterol Salts Compared to Placebo Measured by Forced Vital Capacity (FVC)
2 hour
|
3.5789 liter
Interval 3.2548 to 3.9031
|
3.5992 liter
Interval 3.2751 to 3.9233
|
3.3987 liter
Interval 3.0745 to 3.7228
|
|
Bronchodilator Effect of Indacaterol Salts Compared to Placebo Measured by Forced Vital Capacity (FVC)
8 hour
|
3.5670 liter
Interval 3.2428 to 3.8913
|
3.5617 liter
Interval 3.2376 to 3.8858
|
3.3680 liter
Interval 3.0438 to 3.6922
|
|
Bronchodilator Effect of Indacaterol Salts Compared to Placebo Measured by Forced Vital Capacity (FVC)
23 hour 15 min
|
3.6055 liter
Interval 3.2812 to 3.9298
|
3.5448 liter
Interval 3.2207 to 3.8689
|
3.4199 liter
Interval 3.0952 to 3.7446
|
SECONDARY outcome
Timeframe: Day 14 of each of the three treatment periods at 5, 15, 30m, 1 2, 3, 4, 8, 12, 23hour.15min and 23hour.45minPopulation: The PD analysis set included all patients with available PD parameter data who received any study drug and experienced no major protocol deviations with relevant impact on PD data
Forced Vital Capacity is the amount of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. FVC was assessed by spirometry at each post dose time point after 14 days. A positive change from baseline in FVC indicates improvement in lung function.
Outcome measures
| Measure |
Indacaterol Maleate
n=51 Participants
indacaterol maleate 150 μg via Breezhaler
|
Indacaterol Acetate
n=52 Participants
indacaterol acetate 150 μg via Breezhaler
|
Placebo
n=53 Participants
matching placebo capsules to indacaterol via Breezhaler
|
|---|---|---|---|
|
Bronchodilator Effect of Indacaterol Salts Compared to Placebo Measured by FVC (% Predicted)
5 min
|
90.4 Percentage of predicted FVC
Interval 86.1 to 94.6
|
91.2 Percentage of predicted FVC
Interval 86.9 to 95.4
|
85.3 Percentage of predicted FVC
Interval 81.1 to 89.6
|
|
Bronchodilator Effect of Indacaterol Salts Compared to Placebo Measured by FVC (% Predicted)
15 min
|
90.8 Percentage of predicted FVC
Interval 86.6 to 95.1
|
90.7 Percentage of predicted FVC
Interval 86.5 to 95.0
|
84.9 Percentage of predicted FVC
Interval 80.6 to 89.1
|
|
Bronchodilator Effect of Indacaterol Salts Compared to Placebo Measured by FVC (% Predicted)
30 min
|
91.6 Percentage of predicted FVC
Interval 87.4 to 95.9
|
91.4 Percentage of predicted FVC
Interval 87.2 to 95.7
|
85.1 Percentage of predicted FVC
Interval 80.8 to 89.3
|
|
Bronchodilator Effect of Indacaterol Salts Compared to Placebo Measured by FVC (% Predicted)
1 hour
|
91.1 Percentage of predicted FVC
Interval 86.8 to 95.3
|
91.1 Percentage of predicted FVC
Interval 86.9 to 95.3
|
85.6 Percentage of predicted FVC
Interval 81.4 to 89.8
|
|
Bronchodilator Effect of Indacaterol Salts Compared to Placebo Measured by FVC (% Predicted)
2 hours
|
90.7 Percentage of predicted FVC
Interval 86.4 to 94.9
|
91.4 Percentage of predicted FVC
Interval 87.1 to 95.6
|
85.9 Percentage of predicted FVC
Interval 81.7 to 90.2
|
|
Bronchodilator Effect of Indacaterol Salts Compared to Placebo Measured by FVC (% Predicted)
4 hours
|
90.5 Percentage of predicted FVC
Interval 86.3 to 94.8
|
91.3 Percentage of predicted FVC
Interval 87.0 to 95.5
|
86.2 Percentage of predicted FVC
Interval 82.0 to 90.5
|
|
Bronchodilator Effect of Indacaterol Salts Compared to Placebo Measured by FVC (% Predicted)
8 hours
|
90.4 Percentage of predicted FVC
Interval 86.1 to 94.6
|
90.3 Percentage of predicted FVC
Interval 86.1 to 94.6
|
85.4 Percentage of predicted FVC
Interval 81.1 to 89.6
|
|
Bronchodilator Effect of Indacaterol Salts Compared to Placebo Measured by FVC (% Predicted)
12 hours
|
88.5 Percentage of predicted FVC
Interval 84.3 to 92.8
|
88.2 Percentage of predicted FVC
Interval 84.0 to 92.5
|
84 Percentage of predicted FVC
Interval 79.8 to 88.3
|
|
Bronchodilator Effect of Indacaterol Salts Compared to Placebo Measured by FVC (% Predicted)
23 hours 15 min
|
91.5 Percentage of predicted FVC
Interval 87.2 to 95.7
|
89.9 Percentage of predicted FVC
Interval 85.6 to 94.1
|
86.9 Percentage of predicted FVC
Interval 82.6 to 91.2
|
|
Bronchodilator Effect of Indacaterol Salts Compared to Placebo Measured by FVC (% Predicted)
23 hours 45 min
|
90.6 Percentage of predicted FVC
Interval 86.4 to 94.9
|
90.6 Percentage of predicted FVC
Interval 86.4 to 94.9
|
86.5 Percentage of predicted FVC
Interval 82.3 to 90.8
|
SECONDARY outcome
Timeframe: Day 14 of each of the three treatment periods at 5, 15, 30m, 1 2, 3, 4, 8, 12, 23hour.15min and 23hour.45minPopulation: The PD analysis set included all patients with available PD parameter data who received any study drug and experienced no major protocol deviations with relevant impact on PD data
Bronchodilator effect of indacaterol salts compared to placebo in terms of FEV1/FVC at each post dose time point after 14 days. FEV1/FVC ratio is the percentage of the total FVC that is expelled from the lungs during the first second of forced exhalation.
Outcome measures
| Measure |
Indacaterol Maleate
n=51 Participants
indacaterol maleate 150 μg via Breezhaler
|
Indacaterol Acetate
n=52 Participants
indacaterol acetate 150 μg via Breezhaler
|
Placebo
n=53 Participants
matching placebo capsules to indacaterol via Breezhaler
|
|---|---|---|---|
|
Bronchodilator Effect of Indacaterol Salts Compared to Placebo Measured by FEV1/FVC
15 min
|
0.7002 Ratio
Interval 0.6751 to 0.7253
|
0.7017 Ratio
Interval 0.6766 to 0.7268
|
0.6672 Ratio
Interval 0.6421 to 0.6923
|
|
Bronchodilator Effect of Indacaterol Salts Compared to Placebo Measured by FEV1/FVC
30 min
|
0.7012 Ratio
Interval 0.6761 to 0.7263
|
0.6996 Ratio
Interval 0.6745 to 0.7246
|
0.6706 Ratio
Interval 0.6455 to 0.6957
|
|
Bronchodilator Effect of Indacaterol Salts Compared to Placebo Measured by FEV1/FVC
4 hour
|
0.7057 Ratio
Interval 0.6806 to 0.7308
|
0.7010 Ratio
Interval 0.6759 to 0.7261
|
0.6732 Ratio
Interval 0.6481 to 0.6984
|
|
Bronchodilator Effect of Indacaterol Salts Compared to Placebo Measured by FEV1/FVC
8 hour
|
0.6962 Ratio
Interval 0.671 to 0.7213
|
0.6967 Ratio
Interval 0.6716 to 0.7218
|
0.6651 Ratio
Interval 0.6399 to 0.6902
|
|
Bronchodilator Effect of Indacaterol Salts Compared to Placebo Measured by FEV1/FVC
12 hour
|
0.6958 Ratio
Interval 0.6707 to 0.721
|
0.6885 Ratio
Interval 0.6634 to 0.7135
|
0.6599 Ratio
Interval 0.6348 to 0.6851
|
|
Bronchodilator Effect of Indacaterol Salts Compared to Placebo Measured by FEV1/FVC
5 min
|
0.6979 Ratio
Interval 0.6728 to 0.723
|
0.6952 Ratio
Interval 0.6701 to 0.7202
|
0.6729 Ratio
Interval 0.6478 to 0.6981
|
|
Bronchodilator Effect of Indacaterol Salts Compared to Placebo Measured by FEV1/FVC
1 hour
|
0.7053 Ratio
Interval 0.6802 to 0.7304
|
0.7007 Ratio
Interval 0.6757 to 0.7258
|
0.6729 Ratio
Interval 0.6478 to 0.698
|
|
Bronchodilator Effect of Indacaterol Salts Compared to Placebo Measured by FEV1/FVC
2 hour
|
0.7085 Ratio
Interval 0.6834 to 0.7336
|
0.7085 Ratio
Interval 0.6834 to 0.7335
|
0.6747 Ratio
Interval 0.6496 to 0.6998
|
|
Bronchodilator Effect of Indacaterol Salts Compared to Placebo Measured by FEV1/FVC
23 hour 15 min
|
0.6898 Ratio
Interval 0.6647 to 0.715
|
0.6853 Ratio
Interval 0.6602 to 0.7104
|
0.6572 Ratio
Interval 0.632 to 0.6825
|
|
Bronchodilator Effect of Indacaterol Salts Compared to Placebo Measured by FEV1/FVC
23 hour 45 min
|
0.6934 Ratio
Interval 0.6683 to 0.7186
|
0.6899 Ratio
Interval 0.6648 to 0.715
|
0.6633 Ratio
Interval 0.6381 to 0.6886
|
SECONDARY outcome
Timeframe: Day 14 of each of the three treatment periods at 5, 15, 30m, 1 2, 3, 4, 8, 12, 23hour.15min and 23hour.45minPopulation: The PD analysis set included all patients with available PD parameter data who received any study drug and experienced no major protocol deviations with relevant impact on PD data
The Forced Expiratory Flow (FEF) 25%-75% measurement describes the amount of air expelled from the lungs during the middle half (25% - 75%) of the forced vital capacity test and is measured using spirometry at each post dose time point after 14 days
Outcome measures
| Measure |
Indacaterol Maleate
n=51 Participants
indacaterol maleate 150 μg via Breezhaler
|
Indacaterol Acetate
n=52 Participants
indacaterol acetate 150 μg via Breezhaler
|
Placebo
n=53 Participants
matching placebo capsules to indacaterol via Breezhaler
|
|---|---|---|---|
|
Bronchodilator Effect of Indacaterol Salts Compared to Placebo Measured by FEF25-75%
5 min
|
1.6968 Liters/second
Interval 1.4675 to 1.9261
|
1.6918 Liters/second
Interval 1.4628 to 1.9208
|
1.4962 Liters/second
Interval 1.2668 to 1.7256
|
|
Bronchodilator Effect of Indacaterol Salts Compared to Placebo Measured by FEF25-75%
15 min
|
1.7454 Liters/second
Interval 1.516 to 1.9747
|
1.7458 Liters/second
Interval 1.5165 to 1.9751
|
1.4531 Liters/second
Interval 1.2238 to 1.6824
|
|
Bronchodilator Effect of Indacaterol Salts Compared to Placebo Measured by FEF25-75%
30 min
|
1.7347 Liters/second
Interval 1.5053 to 1.964
|
1.7413 Liters/second
Interval 1.5122 to 1.9704
|
1.4690 Liters/second
Interval 1.2397 to 1.6983
|
|
Bronchodilator Effect of Indacaterol Salts Compared to Placebo Measured by FEF25-75%
1 hour
|
1.7715 Liters/second
Interval 1.5422 to 2.0008
|
1.7349 Liters/second
Interval 1.5059 to 1.964
|
1.4963 Liters/second
Interval 1.267 to 1.7256
|
|
Bronchodilator Effect of Indacaterol Salts Compared to Placebo Measured by FEF25-75%
2 hour
|
1.7907 Liters/second
Interval 1.5613 to 2.02
|
1.8074 Liters/second
Interval 1.5782 to 2.0365
|
1.5088 Liters/second
Interval 1.2795 to 1.7381
|
|
Bronchodilator Effect of Indacaterol Salts Compared to Placebo Measured by FEF25-75%
4 hour
|
1.7663 Liters/second
Interval 1.537 to 1.9956
|
1.7503 Liters/second
Interval 1.5212 to 1.9795
|
1.4843 Liters/second
Interval 1.2549 to 1.7137
|
|
Bronchodilator Effect of Indacaterol Salts Compared to Placebo Measured by FEF25-75%
8 hour
|
1.6755 Liters/second
Interval 1.446 to 1.905
|
1.6774 Liters/second
Interval 1.4483 to 1.9066
|
1.4217 Liters/second
Interval 1.1922 to 1.6512
|
|
Bronchodilator Effect of Indacaterol Salts Compared to Placebo Measured by FEF25-75%
12 hour
|
1.6549 Liters/second
Interval 1.4254 to 1.8844
|
1.5849 Liters/second
Interval 1.3557 to 1.814
|
1.3862 Liters/second
Interval 1.1566 to 1.6158
|
|
Bronchodilator Effect of Indacaterol Salts Compared to Placebo Measured by FEF25-75%
23 hour 15 min
|
1.6667 Liters/second
Interval 1.437 to 1.8964
|
1.6257 Liters/second
Interval 1.3965 to 1.855
|
1.4214 Liters/second
Interval 1.191 to 1.6518
|
|
Bronchodilator Effect of Indacaterol Salts Compared to Placebo Measured by FEF25-75%
23 hour 45 min
|
1.6446 Liters/second
Interval 1.4149 to 1.8743
|
1.6580 Liters/second
Interval 1.4288 to 1.8873
|
1.4584 Liters/second
Interval 1.228 to 1.6866
|
SECONDARY outcome
Timeframe: Pre-dose to 4 hours post-dose on Day 14 of each of the three treatment periodsPopulation: The PD analysis set included all patients with available PD parameter data who received any study drug and experienced no major protocol deviations with relevant impact on PD data
Standardized FEV1 AUC from pre-dose to 4 h post-dose. Evaluated the differences in standardized FEV1 AUC0-4h (L) after 14 days of treatment between indacaterol maleate 150 μg and placebo, and between indacaterol acetate 150 μg and placebo. FEV1 was measured with spirometry conducted according to internationally accepted standards. The standardized AUC FEV1 was calculated as the sum of trapezoids divided by the length of time over an entire day (AUC 0-4h)
Outcome measures
| Measure |
Indacaterol Maleate
n=51 Participants
indacaterol maleate 150 μg via Breezhaler
|
Indacaterol Acetate
n=52 Participants
indacaterol acetate 150 μg via Breezhaler
|
Placebo
n=51 Participants
matching placebo capsules to indacaterol via Breezhaler
|
|---|---|---|---|
|
Bronchodilator Effect of Indacaterol Salts Compared to Placebo in Standardized FEV1 AUC.
|
2.5179 Liters
Standard Error 0.11213
|
2.5151 Liters
Standard Error 0.11205
|
2.2703 Liters
Standard Error 0.11213
|
SECONDARY outcome
Timeframe: 14 days of treatment for each of the three treatment periodsPopulation: The PD analysis set included all patients with available PD parameter data who received any study drug and experienced no major protocol deviations with relevant impact on PD data
The mean daily number of puffs of rescue medication usage as reported by subjects via diary.
Outcome measures
| Measure |
Indacaterol Maleate
n=51 Participants
indacaterol maleate 150 μg via Breezhaler
|
Indacaterol Acetate
n=52 Participants
indacaterol acetate 150 μg via Breezhaler
|
Placebo
n=51 Participants
matching placebo capsules to indacaterol via Breezhaler
|
|---|---|---|---|
|
Rescue Medication Usage
|
1.01 Puffs
Standard Error 0.228
|
1.01 Puffs
Standard Error 0.227
|
1.43 Puffs
Standard Error 0.228
|
SECONDARY outcome
Timeframe: Days 8 through Day 14 of each of the three treatment periodsPopulation: The PD analysis set included all patients with available PD parameter data who received any study drug and experienced no major protocol deviations with relevant impact on PD data
A Peak Expiratory Flow (PEF) meter was distributed to patients at Visit 1, to be used to measure PEF twice-daily as directed. During the Screening and Treatment Periods, PEF was measured in the morning and evening every day. the morning PEF was performed within 15 minutes after waking, and the evening PEF approximately 12 hours later. The highest of 3 values was recorded as the daily personal best. The personal best was used to calculate the mean morning PEF and mean evening PEF value collected between assessment Visits LS Mean of change from baseline in mean morning PEF is calculated with the ANOVA model using treatment, stratification group, dosing schedule, gender, center grouping, smoking status, and baseline mean morning PEF as covariates
Outcome measures
| Measure |
Indacaterol Maleate
n=51 Participants
indacaterol maleate 150 μg via Breezhaler
|
Indacaterol Acetate
n=52 Participants
indacaterol acetate 150 μg via Breezhaler
|
Placebo
n=51 Participants
matching placebo capsules to indacaterol via Breezhaler
|
|---|---|---|---|
|
Mean Overall Peak Expiratory Flow (PEF)
|
409.7 Liters/min
Standard Error 15.06
|
407.6 Liters/min
Standard Error 15.05
|
376.8 Liters/min
Standard Error 15.06
|
Adverse Events
Indacaterol Maleate 150 µg
Indacaterol Acetate 150 µg
Placebo
Serious adverse events
| Measure |
Indacaterol Maleate 150 µg
n=51 participants at risk
indacaterol maleate 150 μg via Breezhaler
|
Indacaterol Acetate 150 µg
n=52 participants at risk
indacaterol acetate 150 μg via Breezhaler
|
Placebo
n=53 participants at risk
matching placebo capsules to indacaterol via Breezhaler
|
|---|---|---|---|
|
Infections and infestations
Pharyngitis streptococcal
|
0.00%
0/51 • until 30 days after the last Investigational Product (IP) administration
|
1.9%
1/52 • until 30 days after the last Investigational Product (IP) administration
|
0.00%
0/53 • until 30 days after the last Investigational Product (IP) administration
|
|
Infections and infestations
Sinusitis
|
0.00%
0/51 • until 30 days after the last Investigational Product (IP) administration
|
1.9%
1/52 • until 30 days after the last Investigational Product (IP) administration
|
0.00%
0/53 • until 30 days after the last Investigational Product (IP) administration
|
Other adverse events
| Measure |
Indacaterol Maleate 150 µg
n=51 participants at risk
indacaterol maleate 150 μg via Breezhaler
|
Indacaterol Acetate 150 µg
n=52 participants at risk
indacaterol acetate 150 μg via Breezhaler
|
Placebo
n=53 participants at risk
matching placebo capsules to indacaterol via Breezhaler
|
|---|---|---|---|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/51 • until 30 days after the last Investigational Product (IP) administration
|
1.9%
1/52 • until 30 days after the last Investigational Product (IP) administration
|
0.00%
0/53 • until 30 days after the last Investigational Product (IP) administration
|
|
Gastrointestinal disorders
Vomiting
|
2.0%
1/51 • until 30 days after the last Investigational Product (IP) administration
|
1.9%
1/52 • until 30 days after the last Investigational Product (IP) administration
|
0.00%
0/53 • until 30 days after the last Investigational Product (IP) administration
|
|
Hepatobiliary disorders
Cholangitis
|
0.00%
0/51 • until 30 days after the last Investigational Product (IP) administration
|
0.00%
0/52 • until 30 days after the last Investigational Product (IP) administration
|
1.9%
1/53 • until 30 days after the last Investigational Product (IP) administration
|
|
Infections and infestations
Nasopharyngitis
|
0.00%
0/51 • until 30 days after the last Investigational Product (IP) administration
|
0.00%
0/52 • until 30 days after the last Investigational Product (IP) administration
|
1.9%
1/53 • until 30 days after the last Investigational Product (IP) administration
|
|
Infections and infestations
Sinusitis
|
0.00%
0/51 • until 30 days after the last Investigational Product (IP) administration
|
0.00%
0/52 • until 30 days after the last Investigational Product (IP) administration
|
1.9%
1/53 • until 30 days after the last Investigational Product (IP) administration
|
|
Infections and infestations
Upper respiratory tract infection
|
2.0%
1/51 • until 30 days after the last Investigational Product (IP) administration
|
3.8%
2/52 • until 30 days after the last Investigational Product (IP) administration
|
3.8%
2/53 • until 30 days after the last Investigational Product (IP) administration
|
|
Injury, poisoning and procedural complications
Laceration
|
0.00%
0/51 • until 30 days after the last Investigational Product (IP) administration
|
0.00%
0/52 • until 30 days after the last Investigational Product (IP) administration
|
1.9%
1/53 • until 30 days after the last Investigational Product (IP) administration
|
|
Injury, poisoning and procedural complications
Skin abrasion
|
0.00%
0/51 • until 30 days after the last Investigational Product (IP) administration
|
0.00%
0/52 • until 30 days after the last Investigational Product (IP) administration
|
1.9%
1/53 • until 30 days after the last Investigational Product (IP) administration
|
|
Investigations
Alanine aminotransferase increased
|
0.00%
0/51 • until 30 days after the last Investigational Product (IP) administration
|
1.9%
1/52 • until 30 days after the last Investigational Product (IP) administration
|
0.00%
0/53 • until 30 days after the last Investigational Product (IP) administration
|
|
Investigations
Aspartate aminotransferase increased
|
0.00%
0/51 • until 30 days after the last Investigational Product (IP) administration
|
1.9%
1/52 • until 30 days after the last Investigational Product (IP) administration
|
0.00%
0/53 • until 30 days after the last Investigational Product (IP) administration
|
|
Investigations
Blood potassium increased
|
2.0%
1/51 • until 30 days after the last Investigational Product (IP) administration
|
0.00%
0/52 • until 30 days after the last Investigational Product (IP) administration
|
0.00%
0/53 • until 30 days after the last Investigational Product (IP) administration
|
|
Investigations
Weight increased
|
0.00%
0/51 • until 30 days after the last Investigational Product (IP) administration
|
1.9%
1/52 • until 30 days after the last Investigational Product (IP) administration
|
0.00%
0/53 • until 30 days after the last Investigational Product (IP) administration
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/51 • until 30 days after the last Investigational Product (IP) administration
|
1.9%
1/52 • until 30 days after the last Investigational Product (IP) administration
|
1.9%
1/53 • until 30 days after the last Investigational Product (IP) administration
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/51 • until 30 days after the last Investigational Product (IP) administration
|
1.9%
1/52 • until 30 days after the last Investigational Product (IP) administration
|
0.00%
0/53 • until 30 days after the last Investigational Product (IP) administration
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
0.00%
0/51 • until 30 days after the last Investigational Product (IP) administration
|
1.9%
1/52 • until 30 days after the last Investigational Product (IP) administration
|
0.00%
0/53 • until 30 days after the last Investigational Product (IP) administration
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/51 • until 30 days after the last Investigational Product (IP) administration
|
0.00%
0/52 • until 30 days after the last Investigational Product (IP) administration
|
1.9%
1/53 • until 30 days after the last Investigational Product (IP) administration
|
|
Nervous system disorders
Dizziness
|
2.0%
1/51 • until 30 days after the last Investigational Product (IP) administration
|
0.00%
0/52 • until 30 days after the last Investigational Product (IP) administration
|
0.00%
0/53 • until 30 days after the last Investigational Product (IP) administration
|
|
Nervous system disorders
Headache
|
0.00%
0/51 • until 30 days after the last Investigational Product (IP) administration
|
1.9%
1/52 • until 30 days after the last Investigational Product (IP) administration
|
0.00%
0/53 • until 30 days after the last Investigational Product (IP) administration
|
|
Psychiatric disorders
Anxiety
|
0.00%
0/51 • until 30 days after the last Investigational Product (IP) administration
|
1.9%
1/52 • until 30 days after the last Investigational Product (IP) administration
|
0.00%
0/53 • until 30 days after the last Investigational Product (IP) administration
|
|
Respiratory, thoracic and mediastinal disorders
Asthma
|
0.00%
0/51 • until 30 days after the last Investigational Product (IP) administration
|
1.9%
1/52 • until 30 days after the last Investigational Product (IP) administration
|
0.00%
0/53 • until 30 days after the last Investigational Product (IP) administration
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
23.5%
12/51 • until 30 days after the last Investigational Product (IP) administration
|
0.00%
0/52 • until 30 days after the last Investigational Product (IP) administration
|
1.9%
1/53 • until 30 days after the last Investigational Product (IP) administration
|
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