Asthma
Conditions
Keywords
Indacaterol, asthma, salmeterol
Brief summary
This study compared the 14-day bronchodilator efficacy of indacaterol with that of placebo and salmeterol
Interventions
DRUGIndacaterol
Once daily via Concept1, a single-dose dry powder inhaler (SDDPI) for two week. Dosage varies according to randomization scheme.
DRUGSalmeterol
50 µg Salmeterol twice daily in the morning and in the evening via Diskus®, a MDDPI for 2 weeks.
DRUGPlacebo to Indacaterol
Placebo to Indacaterol once daily in the morning via Concept 1, a SDDPI.
Placebo to Salmeterol twice daily in the morning and in the evening via Diskus®, a multi-dose dry powder inhaler (MDDPI).
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: 1. Receiving daily treatment with inhaled corticosteroid in a regimen that has been stable for at least a month prior to screening 2. Prebronchodilator forced expiratory volume in 1 second (FEV1) at screening ≥50 and ≤90% of predicted normal 3. An increase of ≥12% and ≥200 mL in FEV1 over prebronchodilator value within 30 minutes after inhaling albuterol
Exclusion criteria
* Smoking history \>10 pack-years * Patients with a diagnosis of chronic obstructive pulmonary disease (COPD) * Patients with seasonal allergy whose asthma is likely to deteriorate during the study period * Patients who have experienced a severe asthma attack/exacerbation requiring hospitalization in the 6 months prior to screening * Patients who have had an intubation for a severe asthma exacerbation * Patients who have had an emergency room visit for an asthma attack/asthma exacerbation within 6 weeks prior to screening * Patients who have had a respiratory tract infection within 6 weeks prior to screening * Patients with concomitant pulmonary disease * Patients with diabetes Type I or uncontrolled diabetes Type II * Any patient with lung cancer or a history of lung cancer * Patients with a history of certain cardiovascular comorbid conditions * Patients who have ever received or are currently receiving omalizumab or chronic oral corticosteroid therapy Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Trough Forced Expiratory Volume in 1 Second (FEV1) After 2 Weeks of Treatment | Day 15 (after 2 weeks of treatment) | Spirometry was conducted according to internationally accepted standards. The trough FEV1 was defined as the average of the FEV1 measurements taken at 23 hours 10 minutes and 23 hours 45 minutes post dose. The mixed model used baseline FEV1 and FEV1 prior to and 30 minutes post inhalation of albuterol as covariates. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Trough Forced Expiratory Volume in 1 Second (FEV1) After 1 Day of Treatment | Day 2 (after 1 day of treatment) | Spirometry was conducted according to internationally accepted standards. The trough FEV1 was defined as the average of the FEV1 measurements taken at 23 hours 10 minutes and 23 hours 45 minutes post dose on day 2. The mixed model used baseline FEV1 and FEV1 prior to and 30 minutes post inhalation of albuterol as covariates. |
Countries
United States
Participant flow
Pre-assignment details
The study consisted of a 14 day run-in period. 511 participants were randomized but only 502 participants received study drug.
Participants by arm
| Arm | Count |
|---|---|
| Indacaterol 18.75 µg Indacaterol 18.75 µg once daily in the morning via Concept1, a single-dose dry powder inhaler (SDDPI) and Placebo to Salmeterol in the morning and in the evening via Diskus®, a multi-dose dry powder inhaler (MDDPI) for 2 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) albuterol was available for rescue use throughout the study | 84 |
| Indacaterol 37.5 µg Indacaterol 37.5 µg once daily in the morning via Concept1, a SDDPI and Placebo to Salmeterol in the morning and in the evening via Diskus®, a MDDPI for 2 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) albuterol was available for rescue use throughout the study. | 81 |
| Indacaterol 75 µg Indacaterol 75 µg once daily in the morning via Concept1, a SDDPI and Placebo to Salmeterol in the morning and in the evening via Diskus®, a MDDPI for 2 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) albuterol was available for rescue use throughout the study. | 84 |
| Indacaterol 150 µg Indacaterol 150 µg once daily in the morning via Concept1, a SDDPI and Placebo to Salmeterol in the morning and in the evening via Diskus®, MDDPI for 2 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) albuterol was available for rescue use throughout the study. | 85 |
| Salmeterol Salmeterol 50 µg twice daily in the morning and in the evening via Diskus®, a multi-dose dry powder inhaler (MDDPI) and Placebo to Indacaterol once daily in the morning via Concept1, a SDDPI for 2 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) albuterol was available for rescue use throughout the study. | 84 |
| Placebo Placebo to Indacaterol once daily in the morning via Concept 1, a SDDPI and Placebo to Salmeterol in the morning and in the evening via Diskus®, a MDDPI for 2 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) albuterol was available for rescue use throughout the study. | 84 |
| Total | 502 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Abnormal test procedure result(s) | 0 | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Administrative problems | 1 | 3 | 0 | 0 | 0 | 1 |
| Overall Study | Adverse Event | 1 | 1 | 0 | 1 | 5 | 1 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Protocol deviation | 0 | 2 | 1 | 2 | 0 | 0 |
| Overall Study | Unsatisfactory therapeutic effect | 0 | 0 | 0 | 2 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 0 | 0 | 1 | 3 |
Baseline characteristics
| Characteristic | Indacaterol 18.75 µg | Indacaterol 37.5 µg | Indacaterol 75 µg | Indacaterol 150 µg | Salmeterol | Placebo | Total |
|---|---|---|---|---|---|---|---|
| Age Continuous | 42.0 years STANDARD_DEVIATION 14.64 | 41.9 years STANDARD_DEVIATION 14.96 | 40.2 years STANDARD_DEVIATION 14.71 | 41.0 years STANDARD_DEVIATION 15.2 | 40.9 years STANDARD_DEVIATION 14.56 | 40.6 years STANDARD_DEVIATION 14.17 | 41.1 years STANDARD_DEVIATION 14.65 |
| Sex: Female, Male Female | 42 Participants | 46 Participants | 49 Participants | 55 Participants | 46 Participants | 40 Participants | 278 Participants |
| Sex: Female, Male Male | 42 Participants | 35 Participants | 35 Participants | 30 Participants | 38 Participants | 44 Participants | 224 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 | 4 / 84 | 2 / 81 | 12 / 84 | 7 / 85 | 5 / 84 | 4 / 84 |
| serious Total, serious adverse events | 0 / 84 | 0 / 81 | 0 / 84 | 1 / 85 | 0 / 84 | 0 / 84 |
Outcome results
Primary
Trough Forced Expiratory Volume in 1 Second (FEV1) After 2 Weeks of Treatment
Spirometry was conducted according to internationally accepted standards. The trough FEV1 was defined as the average of the FEV1 measurements taken at 23 hours 10 minutes and 23 hours 45 minutes post dose. The mixed model used baseline FEV1 and FEV1 prior to and 30 minutes post inhalation of albuterol as covariates.
Time frame: Day 15 (after 2 weeks of treatment)
Population: Participants from the Full Analysis Set, randomized participants who received at least one dose of study drug, who had efficacy data for this outcome measure. Missing data were imputed last observation carried forward (LOCF).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Indacaterol 18.75 µg | Trough Forced Expiratory Volume in 1 Second (FEV1) After 2 Weeks of Treatment | 2.50 Liters | Standard Error 0.036 |
| Indacaterol 37.5 µg | Trough Forced Expiratory Volume in 1 Second (FEV1) After 2 Weeks of Treatment | 2.52 Liters | Standard Error 0.037 |
| Indacaterol 75 µg | Trough Forced Expiratory Volume in 1 Second (FEV1) After 2 Weeks of Treatment | 2.59 Liters | Standard Error 0.036 |
| Indacaterol 150 µg | Trough Forced Expiratory Volume in 1 Second (FEV1) After 2 Weeks of Treatment | 2.54 Liters | Standard Error 0.037 |
| Salmeterol | Trough Forced Expiratory Volume in 1 Second (FEV1) After 2 Weeks of Treatment | 2.54 Liters | Standard Error 0.037 |
| Placebo | Trough Forced Expiratory Volume in 1 Second (FEV1) After 2 Weeks of Treatment | 2.42 Liters | Standard Error 0.036 |
Secondary
Trough Forced Expiratory Volume in 1 Second (FEV1) After 1 Day of Treatment
Spirometry was conducted according to internationally accepted standards. The trough FEV1 was defined as the average of the FEV1 measurements taken at 23 hours 10 minutes and 23 hours 45 minutes post dose on day 2. The mixed model used baseline FEV1 and FEV1 prior to and 30 minutes post inhalation of albuterol as covariates.
Time frame: Day 2 (after 1 day of treatment)
Population: Participants from the Full Analysis Set, randomized participants who received at least one dose of study drug, who had efficacy data for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Indacaterol 18.75 µg | Trough Forced Expiratory Volume in 1 Second (FEV1) After 1 Day of Treatment | 2.46 Liters | Standard Error 0.026 |
| Indacaterol 37.5 µg | Trough Forced Expiratory Volume in 1 Second (FEV1) After 1 Day of Treatment | 2.52 Liters | Standard Error 0.027 |
| Indacaterol 75 µg | Trough Forced Expiratory Volume in 1 Second (FEV1) After 1 Day of Treatment | 2.54 Liters | Standard Error 0.026 |
| Indacaterol 150 µg | Trough Forced Expiratory Volume in 1 Second (FEV1) After 1 Day of Treatment | 2.60 Liters | Standard Error 0.026 |
| Salmeterol | Trough Forced Expiratory Volume in 1 Second (FEV1) After 1 Day of Treatment | 2.65 Liters | Standard Error 0.027 |
| Placebo | Trough Forced Expiratory Volume in 1 Second (FEV1) After 1 Day of Treatment | 2.45 Liters | Standard Error 0.027 |