Asthma
Conditions
Keywords
wheezing, short of breath, laba, inhaler
Brief summary
The purpose of this study is to determine the efficacy of indacaterol 55µg once daily (and 27.5 µg twice) in QVA149 compared to 75 µg indacaterol monotherapy.
Interventions
DRUGIndacaterol 27.5 mcg
indacaterol 27.5 mcg twice daily inhaled once via inhaler
DRUGIndacaterol 37.5
Indacaterol 37.5 mcg once daily, inhaled once via inhaler
DRUGIndacaterol 55 mcg
Indacaterol 55 mcg once daily, inhaled once via inhaler
DRUGIndacaterol 75 mcg
Indacaterol 75 mcg once daily, inhaled once via inhaler
DRUGIndacaterol 150 mcg
Indacaterol 150 mcg once daily, inhaled once via inhaler
DRUGPlacebo
Placebo to indacaterol once or twice daily (depending on assigned sequence) via inlaher
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Asthma for at least 6 months, using inhaled corticosteroid for at least one month, foreced breath test less than below the normal value of the general population, -show an immediate improvement in breathing when given albuterol
Exclusion criteria
* patients who have smoked in the past 6 months or are currently smoking, including those who smoked more than a pack of cigarettes a day for at least 10 years, -patients who have a history of life-threatening asthma, -patients who have had an astham attack, in the last 6 weeks, requiring use of systemic steroids, hospitalization, or ER visit, -patients who have had a respiratory tract infection or worsening asthma between screening or run-in periods, patients requring use of other asthma-related drugs during the trial, other protocol-defined inclusion/exclusion may apply
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Period Baseline in FEV1 (L) AUC(0-24h) | Day 1 (24 hours) | Forced Expiratory Volume in 1 second (FEV1) is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation. FEV1 will be measured pre-dose and over a 24 hours post-dose period. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Period Baseline in FEV1 (L) AUC(0-12h) and FEV1 (L) AUC(12- 24h) | Day 1 (12 hours) | Forced Expiratory Volume in 1 second (FEV1) is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation. FEV1 will be measured pre-dose and over a 12 hours post-dose period. |
| Change From Period Baseline in Peak FEV1 (L) | Day 1 (24 hours) | Spirometry will be conducted according to internationally accepted standards. Peak Forced Expiratory Volume in 1 second (FEV1) is the maximum FEV1 recorded between different time points. |
| Change From Period Baseline in Trough FEV1 (L) | Day 1 (24 hours) | Forced Expiratory Volume in 1 second (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 trough in FEV1 is defined as the mean of two measurements at different time points. |
| Change From Period Baseline in FVC (L) AUC (0-24h) | Day 1 (24 hours) | Forced Vital Capacity (FVC) is the amount of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. FVC will be assessed via spirometry. A positive change from baseline in FVC indicates improvement in lung function. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| All Participants All participants randomized to one of six treatment sequences | 91 |
| Total | 91 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Protocol deviation | 1 | 1 | 0 | 1 | 3 | 0 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Continuous | 47.4 Years STANDARD_DEVIATION 13.19 |
| Sex: Female, Male Female | 53 Participants |
| Sex: Female, Male Male | 38 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 15 / 88 | 14 / 87 | 10 / 86 | 11 / 85 | 12 / 90 | 9 / 88 |
| serious Total, serious adverse events | 0 / 88 | 1 / 87 | 1 / 86 | 1 / 85 | 0 / 90 | 0 / 88 |
Outcome results
Primary
Change From Period Baseline in FEV1 (L) AUC(0-24h)
Forced Expiratory Volume in 1 second (FEV1) is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation. FEV1 will be measured pre-dose and over a 24 hours post-dose period.
Time frame: Day 1 (24 hours)
Population: drug. Following the intent-to-treat principle, data for patients in the FAS were analyzed according to the treatment they were randomized to in the assigned treatment sequence. The FAS was used in the analysis of all efficacy variables
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Ind 150 μg | Change From Period Baseline in FEV1 (L) AUC(0-24h) | 0.209 Liters | Standard Error 0.0153 |
| Ind 75 μg | Change From Period Baseline in FEV1 (L) AUC(0-24h) | 0.165 Liters | Standard Error 0.0152 |
| Ind 55 μg | Change From Period Baseline in FEV1 (L) AUC(0-24h) | 0.154 Liters | Standard Error 0.0152 |
| Ind 37.5 μg | Change From Period Baseline in FEV1 (L) AUC(0-24h) | 0.121 Liters | Standard Error 0.0153 |
| Ind 27.5 | Change From Period Baseline in FEV1 (L) AUC(0-24h) | 0.143 Liters | Standard Error 0.0151 |
| Placebo | Change From Period Baseline in FEV1 (L) AUC(0-24h) | 0.022 Liters | Standard Error 0.0152 |
Secondary
Change From Period Baseline in FEV1 (L) AUC(0-12h) and FEV1 (L) AUC(12- 24h)
Forced Expiratory Volume in 1 second (FEV1) is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation. FEV1 will be measured pre-dose and over a 12 hours post-dose period.
Time frame: Day 1 (12 hours)
Population: The Full Analysis Set (FAS) consisted of all patients in the RAN who received at least 1 dose of study drug. Following the intent-to-treat principle, data for patients in the FAS were analyzed according to the treatment they were randomized to in the assigned treatment sequence. The FAS was used in the analysis of all efficacy variables
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Ind 150 μg | Change From Period Baseline in FEV1 (L) AUC(0-12h) and FEV1 (L) AUC(12- 24h) | FEV1 AUC (0-12h) | 0.229 liters | Standard Error 0.015 |
| Ind 150 μg | Change From Period Baseline in FEV1 (L) AUC(0-12h) and FEV1 (L) AUC(12- 24h) | FEV1 AUC (12-24h) | 0.190 liters | Standard Error 0.0177 |
| Ind 75 μg | Change From Period Baseline in FEV1 (L) AUC(0-12h) and FEV1 (L) AUC(12- 24h) | FEV1 AUC (0-12h) | 0.180 liters | Standard Error 0.0148 |
| Ind 75 μg | Change From Period Baseline in FEV1 (L) AUC(0-12h) and FEV1 (L) AUC(12- 24h) | FEV1 AUC (12-24h) | 0.153 liters | Standard Error 0.0175 |
| Ind 55 μg | Change From Period Baseline in FEV1 (L) AUC(0-12h) and FEV1 (L) AUC(12- 24h) | FEV1 AUC (0-12h) | 0.176 liters | Standard Error 0.0149 |
| Ind 55 μg | Change From Period Baseline in FEV1 (L) AUC(0-12h) and FEV1 (L) AUC(12- 24h) | FEV1 AUC (12-24h) | 0.136 liters | Standard Error 0.0176 |
| Ind 37.5 μg | Change From Period Baseline in FEV1 (L) AUC(0-12h) and FEV1 (L) AUC(12- 24h) | FEV1 AUC (0-12h) | 0.131 liters | Standard Error 0.015 |
| Ind 37.5 μg | Change From Period Baseline in FEV1 (L) AUC(0-12h) and FEV1 (L) AUC(12- 24h) | FEV1 AUC (12-24h) | 0.115 liters | Standard Error 0.0177 |
| Ind 27.5 | Change From Period Baseline in FEV1 (L) AUC(0-12h) and FEV1 (L) AUC(12- 24h) | FEV1 AUC (0-12h) | 0.125 liters | Standard Error 0.0148 |
| Ind 27.5 | Change From Period Baseline in FEV1 (L) AUC(0-12h) and FEV1 (L) AUC(12- 24h) | FEV1 AUC (12-24h) | 0.164 liters | Standard Error 0.0175 |
| Placebo | Change From Period Baseline in FEV1 (L) AUC(0-12h) and FEV1 (L) AUC(12- 24h) | FEV1 AUC (0-12h) | 0.036 liters | Standard Error 0.0148 |
| Placebo | Change From Period Baseline in FEV1 (L) AUC(0-12h) and FEV1 (L) AUC(12- 24h) | FEV1 AUC (12-24h) | 0.012 liters | Standard Error 0.0175 |
Secondary
Change From Period Baseline in FVC (L) AUC (0-24h)
Forced Vital Capacity (FVC) is the amount of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. FVC will be assessed via spirometry. A positive change from baseline in FVC indicates improvement in lung function.
Time frame: Day 1 (24 hours)
Population: The Full Analysis Set (FAS) consisted of all patients in the RAN who received at least 1 dose of study drug. Following the intent-to-treat principle, data for patients in the FAS were analyzed according to the treatment they were randomized to in the assigned treatment sequence. The FAS was used in the analysis of all efficacy variables
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Ind 150 μg | Change From Period Baseline in FVC (L) AUC (0-24h) | 0.147 Liters | Standard Error 0.0183 |
| Ind 75 μg | Change From Period Baseline in FVC (L) AUC (0-24h) | 0.120 Liters | Standard Error 0.0181 |
| Ind 55 μg | Change From Period Baseline in FVC (L) AUC (0-24h) | 0.118 Liters | Standard Error 0.0182 |
| Ind 37.5 μg | Change From Period Baseline in FVC (L) AUC (0-24h) | 0.085 Liters | Standard Error 0.0183 |
| Ind 27.5 | Change From Period Baseline in FVC (L) AUC (0-24h) | 0.106 Liters | Standard Error 0.018 |
| Placebo | Change From Period Baseline in FVC (L) AUC (0-24h) | 0.016 Liters | Standard Error 0.0181 |
Secondary
Change From Period Baseline in Peak FEV1 (L)
Spirometry will be conducted according to internationally accepted standards. Peak Forced Expiratory Volume in 1 second (FEV1) is the maximum FEV1 recorded between different time points.
Time frame: Day 1 (24 hours)
Population: The Full Analysis Set (FAS) consisted of all patients in the RAN who received at least 1 dose of study drug. Following the intent-to-treat principle, data for patients in the FAS were analyzed according to the treatment they were randomized to in the assigned treatment sequence. The FAS was used in the analysis of all efficacy variables
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Ind 150 μg | Change From Period Baseline in Peak FEV1 (L) | 0.347 Liters | Standard Error 0.0154 |
| Ind 75 μg | Change From Period Baseline in Peak FEV1 (L) | 0.290 Liters | Standard Error 0.0152 |
| Ind 55 μg | Change From Period Baseline in Peak FEV1 (L) | 0.298 Liters | Standard Error 0.0153 |
| Ind 37.5 μg | Change From Period Baseline in Peak FEV1 (L) | 0.249 Liters | Standard Error 0.0154 |
| Ind 27.5 | Change From Period Baseline in Peak FEV1 (L) | 0.259 Liters | Standard Error 0.0152 |
| Placebo | Change From Period Baseline in Peak FEV1 (L) | 0.158 Liters | Standard Error 0.0152 |
Secondary
Change From Period Baseline in Trough FEV1 (L)
Forced Expiratory Volume in 1 second (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 trough in FEV1 is defined as the mean of two measurements at different time points.
Time frame: Day 1 (24 hours)
Population: The Full Analysis Set (FAS) consisted of all patients in the RAN who received at least 1 dose of study drug. Following the intent-to-treat principle, data for patients in the FAS were analyzed according to the treatment they were randomized to in the assigned treatment sequence. The FAS was used in the analysis of all efficacy variables
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Ind 150 μg | Change From Period Baseline in Trough FEV1 (L) | 0.207 Liters | Standard Error 0.0183 |
| Ind 75 μg | Change From Period Baseline in Trough FEV1 (L) | 0.162 Liters | Standard Error 0.018 |
| Ind 55 μg | Change From Period Baseline in Trough FEV1 (L) | 0.137 Liters | Standard Error 0.0181 |
| Ind 37.5 μg | Change From Period Baseline in Trough FEV1 (L) | 0.128 Liters | Standard Error 0.0182 |
| Ind 27.5 | Change From Period Baseline in Trough FEV1 (L) | 0.161 Liters | Standard Error 0.018 |
| Placebo | Change From Period Baseline in Trough FEV1 (L) | 0.024 Liters | Standard Error 0.018 |