Efficacy, Safety and Pharmacokinetics of Different Regimens of Indacaterol

Study Overview
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Brief Summary
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This study assessed the bronchodilator efficacy of three different regimens of indacaterol in patients with asthma

Official Title
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A Multi-center, Randomized, Double-blind, Placebo-controlled, Parallel Group, Repeated-dose Study to Evaluate the Efficacy, Safety, Tolerability, and Pharmacokinetics of Three Different Dosing Regimens of Inhaled Indacaterol Maleate in Patients With Persistent Asthma

Conditions
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Persistent Asthma

Intervention / Treatment
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* Drug: Indacaterol
* Drug: Placebo to Indacaterol


Participation Criteria
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Eligibility Criteria
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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/exclusion criteria may apply

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Indacaterol 37.5 µg (twice a day)<br>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. | Drug: Indacaterol<br>* Indacaterol inhaled via Concept1, a single dose dry powder inhaler (SDDPI) for 16 days. Dosage and frequency varied according to randomization scheme.<br>|
| Experimental: Indacaterol 75 µg (once a day)<br>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. | Drug: Indacaterol<br>* Indacaterol inhaled via Concept1, a single dose dry powder inhaler (SDDPI) for 16 days. Dosage and frequency varied according to randomization scheme.<br>Drug: Placebo to Indacaterol<br>* Placebo inhaled via Concept1, a SDDPI. Frequency varied according to randomization scheme.<br>|
| Experimental: Indacaterol 150 µg (every other day)<br>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. | Drug: Indacaterol<br>* Indacaterol inhaled via Concept1, a single dose dry powder inhaler (SDDPI) for 16 days. Dosage and frequency varied according to randomization scheme.<br>Drug: Placebo to Indacaterol<br>* Placebo inhaled via Concept1, a SDDPI. Frequency varied according to randomization scheme.<br>|
| Placebo Comparator: Placebo<br>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. | Drug: Placebo to Indacaterol<br>* Placebo inhaled via Concept1, a SDDPI. Frequency varied according to randomization scheme.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Baseline to week 2 | 
| 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. | Baseline, 0-24 hours post dose week 2 | 
| 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. | Baseline, 0 to 48 hours post dose week 2 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Baseline, 0 to 12 hours post dose week 2 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Indacaterol, Asthma, Bronchodilation, Beta-agonist