Persistent Asthma
Conditions
Keywords
Indacaterol, Asthma, Bronchodilation, Beta-agonist
Brief summary
This study assessed the bronchodilator efficacy of three different regimens of indacaterol in patients with asthma
Interventions
DRUGIndacaterol
Indacaterol inhaled via Concept1, a single dose dry powder inhaler (SDDPI) for 16 days. Dosage and frequency varied according to randomization scheme.
DRUGPlacebo to Indacaterol
Placebo inhaled via Concept1, a SDDPI. Frequency varied according to randomization scheme.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients with a diagnosis of asthma and: * Receiving daily treatment with inhaled corticosteroid in a regimen that has been stable for at least a month prior to screening * FEV1 ≥50% and ≤90% of predicted normal at screening * An increase of ≥12% and ≥200 mL in FEV1 over prebronchodilator value within 30 minutes after inhaling a total dose of albuterol/salbutamol of 360/400 MDI
Exclusion criteria
* Smoking history of ≥ 10 years * Patients with a diagnosis of COPD * Patients who have been previously intubated for a severe asthma exacerbation/ attack * Patients who have experienced a severe asthma attack/exacerbation requiring hospitalization in the 6 months prior to screening * Patients who have had an emergency room visit for an asthma attack/exacerbation within 6 weeks prior to screening * Patients who have had a respiratory tract infection within 6 weeks prior to screening * Patients with seasonal allergy whose asthma is likely to deteriorate during the study period * Patients with Type I or uncontrolled Type II diabetes mellitus Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Trough Forced Expiratory Volume in One Second (FEV1) After Two Weeks of Treatment | Baseline to week 2 | Spirometry was conducted according to internationally accepted standards. Trough FEV1 values were calculated as the mean of the 23.17 hours and 23.75 hours post morning dose FEV1 measurements. Analysis of covariance model was used with baseline FEV1 as a continuous covariate. |
| Change From Baseline in the Forced Expiratory Volume in 1 Second Standardized (With Respect to Time) Area Under the Curve (AUC) From 0 to 24 Hours Post Dose (FEV1 AUC 0-24h) After Two Weeks of Treatment | Baseline, 0-24 hours post dose week 2 | Spirometry was conducted according to internationally accepted standards. Standardized area under the curve (AUC 0-24 hours) of FEV1 measurements taken at pre-dose to 24 hours post-dose was calculated based on the trapezoidal rule and was adjusted for the area per time unit using the scheduled time of measurements for FEV1. Analysis of covariance model was used with baseline FEV1 as a continuous covariate. |
| Change From Baseline in the Forced Expiratory Volume in 1 Second Standardized (With Respect to Time) Area Under the Curve (AUC) From 0 to 48 Hours (FEV1 AUC 0-48h) After Two Weeks of Treatment | Baseline, 0 to 48 hours post dose week 2 | Spirometry was conducted according to internationally accepted standards. Standardized area under the curve (AUC 0-48 hours) of FEV1 measurements taken at pre-dose to 48 hours post-dose was calculated based on the trapezoidal rule and was adjusted for the area per time unit by using the scheduled time of measurements for FEV1. Analysis of covariance model was used with baseline FEV1 as a continuous covariate. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Forced Expiratory Volume in 1 Second Standardized (With Respect to Time) Area Under the Curve (AUC) From 0 to 12 Hours (FEV1 AUC 0-12h) After Two Weeks of Treatment | Baseline, 0 to 12 hours post dose week 2 | Spirometry was conducted according to internationally accepted standards. Standardized area under the curve (AUC 0-12 hours) of FEV1 measurements taken at pre-dose to 12 hours post-dose was calculated based on the trapezoidal rule and was adjusted for the area per time unit by using the scheduled time of measurements for FEV1. Analysis of covariance model was used with baseline FEV1 as a continuous covariate. |
Countries
France, Germany, Jordan, Netherlands, United Kingdom, United States
Participant flow
Pre-assignment details
The study consisted of a 21 day screening period, a 14 day run-in period and a baseline assessment day prior to the 16 day treatment period. 1 participant randomized to 75 ug Indacaterol and 1 participant randomized to Placebo did not receive study drug and were not included in the Safety set milestone.
Participants by arm
| Arm | Count |
|---|---|
| Indacaterol 37.5 µg (Twice a Day) Indacaterol 37.5 µg twice a day (bid) inhaled via Concept1, a single dose dry powder inhaler (SDDPI), in the morning and in the evening for 16 days. All patients had to receive daily treatment with inhaled corticosteroid up to the maximum dose per day in a stable regimen for at least 4-weeks prior to screening and remain stable through out the study. The short acting (beta) β2-agonist (SABA) salbutamol/albuterol was available for rescue use throughout the study. | 48 |
| Indacaterol 75 µg (Once a Day) Indacaterol 75 µg once a day (qd) inhaled via Concept1, a single dose dry powder inhaler (SDDPI), in the morning and Placebo to Indacaterol inhaled once daily via Concept1 in the evening for 16 days. All patients had to receive daily treatment with inhaled corticosteroid up to the maximum dose per day in a stable regimen for at least 4-weeks prior to screening and remain stable through out the study. The short acting (beta) β2-agonist (SABA) salbutamol/albuterol was available for rescue use throughout the study. | 47 |
| Indacaterol 150 µg (Every Other Day) Indacaterol 150 µg every other day (qod) inhaled via Concept1, a single dose dry powder inhaler (SDDPI) for a total of 16 days. Indacaterol 150 µg inhaled via Concept1, a SDDPI, in the morning and Placebo to Indacaterol inhaled via Concept1 in the evening on odd days; and Placebo to Indacaterol inhaled via Concept1 in the morning and in the evening on even days. All patients had to receive daily treatment with inhaled corticosteroid up to the maximum dose per day in a stable regimen for at least 4-weeks prior to screening and remain stable through out the study. The short acting (beta) β2-agonist (SABA) salbutamol/albuterol was available for rescue use throughout the study. | 48 |
| Placebo Placebo to Indacaterol twice daily (bid) inhaled via Concept1, a single dose dry powder inhaler (SDDPI), in the morning and in the evening for 16 days. All patients had to receive daily treatment with inhaled corticosteroid up to the maximum dose per day in a stable regimen for at least 4-weeks prior to screening and remain stable through out the study. The short acting (beta) β2-agonist (SABA) salbutamol/albuterol was available for rescue use throughout the study. | 46 |
| Total | 189 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Abnormal test procedure result(s) | 0 | 1 | 2 | 2 |
| Overall Study | Administrative problems | 0 | 1 | 0 | 1 |
| Overall Study | Adverse Event | 0 | 0 | 1 | 1 |
| Overall Study | Lost to Follow-up | 0 | 0 | 1 | 0 |
| Overall Study | Protocol deviation | 2 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 2 | 2 |
Baseline characteristics
| Characteristic | Indacaterol 37.5 µg (Twice a Day) | Indacaterol 75 µg (Once a Day) | Indacaterol 150 µg (Every Other Day) | Placebo | Total |
|---|---|---|---|---|---|
| Age Continuous | 37.4 years STANDARD_DEVIATION 11 | 41.1 years STANDARD_DEVIATION 14.7 | 42.0 years STANDARD_DEVIATION 12.2 | 40.8 years STANDARD_DEVIATION 12.7 | 40.3 years STANDARD_DEVIATION 12.7 |
| Sex: Female, Male Female | 21 Participants | 24 Participants | 16 Participants | 18 Participants | 79 Participants |
| Sex: Female, Male Male | 27 Participants | 23 Participants | 32 Participants | 28 Participants | 110 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 7 / 48 | 8 / 47 | 11 / 48 | 8 / 46 |
| serious Total, serious adverse events | 0 / 48 | 0 / 47 | 1 / 48 | 0 / 46 |
Outcome results
Primary
Change From Baseline in the Forced Expiratory Volume in 1 Second Standardized (With Respect to Time) Area Under the Curve (AUC) From 0 to 24 Hours Post Dose (FEV1 AUC 0-24h) After Two Weeks of Treatment
Spirometry was conducted according to internationally accepted standards. Standardized area under the curve (AUC 0-24 hours) of FEV1 measurements taken at pre-dose to 24 hours post-dose was calculated based on the trapezoidal rule and was adjusted for the area per time unit using the scheduled time of measurements for FEV1. Analysis of covariance model was used with baseline FEV1 as a continuous covariate.
Time frame: Baseline, 0-24 hours post dose week 2
Population: Pharmacodynamic (PD) Analysis Set included all randomized participants who received at least one dose of study drug and who had evaluable PD data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Indacaterol 37.5 µg (Twice a Day) | Change From Baseline in the Forced Expiratory Volume in 1 Second Standardized (With Respect to Time) Area Under the Curve (AUC) From 0 to 24 Hours Post Dose (FEV1 AUC 0-24h) After Two Weeks of Treatment | 0.196 Liters |
| Indacaterol 75 µg (Once a Day) | Change From Baseline in the Forced Expiratory Volume in 1 Second Standardized (With Respect to Time) Area Under the Curve (AUC) From 0 to 24 Hours Post Dose (FEV1 AUC 0-24h) After Two Weeks of Treatment | 0.198 Liters |
| Indacaterol 150 µg (Every Other Day) | Change From Baseline in the Forced Expiratory Volume in 1 Second Standardized (With Respect to Time) Area Under the Curve (AUC) From 0 to 24 Hours Post Dose (FEV1 AUC 0-24h) After Two Weeks of Treatment | 0.030 Liters |
Primary
Change From Baseline in the Forced Expiratory Volume in 1 Second Standardized (With Respect to Time) Area Under the Curve (AUC) From 0 to 48 Hours (FEV1 AUC 0-48h) After Two Weeks of Treatment
Spirometry was conducted according to internationally accepted standards. Standardized area under the curve (AUC 0-48 hours) of FEV1 measurements taken at pre-dose to 48 hours post-dose was calculated based on the trapezoidal rule and was adjusted for the area per time unit by using the scheduled time of measurements for FEV1. Analysis of covariance model was used with baseline FEV1 as a continuous covariate.
Time frame: Baseline, 0 to 48 hours post dose week 2
Population: Pharmacodynamic (PD) Analysis Set included all randomized participants who received at least one dose of study drug and who had evaluable PD data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Indacaterol 37.5 µg (Twice a Day) | Change From Baseline in the Forced Expiratory Volume in 1 Second Standardized (With Respect to Time) Area Under the Curve (AUC) From 0 to 48 Hours (FEV1 AUC 0-48h) After Two Weeks of Treatment | 0.218 Liters |
| Indacaterol 75 µg (Once a Day) | Change From Baseline in the Forced Expiratory Volume in 1 Second Standardized (With Respect to Time) Area Under the Curve (AUC) From 0 to 48 Hours (FEV1 AUC 0-48h) After Two Weeks of Treatment | 0.198 Liters |
| Indacaterol 150 µg (Every Other Day) | Change From Baseline in the Forced Expiratory Volume in 1 Second Standardized (With Respect to Time) Area Under the Curve (AUC) From 0 to 48 Hours (FEV1 AUC 0-48h) After Two Weeks of Treatment | 0.059 Liters |
Primary
Change From Baseline in the Trough Forced Expiratory Volume in One Second (FEV1) After Two Weeks of Treatment
Spirometry was conducted according to internationally accepted standards. Trough FEV1 values were calculated as the mean of the 23.17 hours and 23.75 hours post morning dose FEV1 measurements. Analysis of covariance model was used with baseline FEV1 as a continuous covariate.
Time frame: Baseline to week 2
Population: Pharmacodynamic (PD) Analysis Set included all randomized participants who received at least one dose of study drug and who had evaluable PD data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Indacaterol 37.5 µg (Twice a Day) | Change From Baseline in the Trough Forced Expiratory Volume in One Second (FEV1) After Two Weeks of Treatment | 0.156 Liters |
| Indacaterol 75 µg (Once a Day) | Change From Baseline in the Trough Forced Expiratory Volume in One Second (FEV1) After Two Weeks of Treatment | 0.197 Liters |
| Indacaterol 150 µg (Every Other Day) | Change From Baseline in the Trough Forced Expiratory Volume in One Second (FEV1) After Two Weeks of Treatment | 0.199 Liters |
| Placebo | Change From Baseline in the Trough Forced Expiratory Volume in One Second (FEV1) After Two Weeks of Treatment | -0.005 Liters |
Secondary
Change From Baseline in the Forced Expiratory Volume in 1 Second Standardized (With Respect to Time) Area Under the Curve (AUC) From 0 to 12 Hours (FEV1 AUC 0-12h) After Two Weeks of Treatment
Spirometry was conducted according to internationally accepted standards. Standardized area under the curve (AUC 0-12 hours) of FEV1 measurements taken at pre-dose to 12 hours post-dose was calculated based on the trapezoidal rule and was adjusted for the area per time unit by using the scheduled time of measurements for FEV1. Analysis of covariance model was used with baseline FEV1 as a continuous covariate.
Time frame: Baseline, 0 to 12 hours post dose week 2
Population: Pharmacodynamic (PD) Analysis Set included all randomized participants who received at least one dose of study drug and who had evaluable PD data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Indacaterol 37.5 µg (Twice a Day) | Change From Baseline in the Forced Expiratory Volume in 1 Second Standardized (With Respect to Time) Area Under the Curve (AUC) From 0 to 12 Hours (FEV1 AUC 0-12h) After Two Weeks of Treatment | 0.245 Liters |
| Indacaterol 75 µg (Once a Day) | Change From Baseline in the Forced Expiratory Volume in 1 Second Standardized (With Respect to Time) Area Under the Curve (AUC) From 0 to 12 Hours (FEV1 AUC 0-12h) After Two Weeks of Treatment | 0.243 Liters |
| Indacaterol 150 µg (Every Other Day) | Change From Baseline in the Forced Expiratory Volume in 1 Second Standardized (With Respect to Time) Area Under the Curve (AUC) From 0 to 12 Hours (FEV1 AUC 0-12h) After Two Weeks of Treatment | 0.059 Liters |