A Study to Evaluate the Effects of Indacaterol Maleate (QAB149) as a New Formulation in the EPIC Test Fixture

Study Overview
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Brief Summary
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This study will assess the pharmacodynamics, safety, tolerability and pharmacokinetics of indacaterol maleate (QAB149), administered via the EPIC test fixture. The study aims to determine whether the novel device has a similar clinical profile as the established concept 1 device.

Official Title
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A Randomized, Double-blind, Double-dummy, Placebo-controlled, 3-period Crossover Study to Evaluate the Pharmacodynamics, Pharmacokinetics, Safety and Tolerability of Orally Inhaled Indacaterol Administered Via the EPIC Test Fixture and the Concept1 Device in Adult Patients With Persistent Asthma

Conditions
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Asthma

Intervention / Treatment
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* Drug: QAB149 75 mg Concept 1
* Drug: QAB149 75 mg Epic Test Fixture
* Other: Placebo Concept 1
* Other: Placebo EPIC Test Fixture


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female patients with asthma, aged 18 or above Patients using inhaled corticosteroid (with or without long acting beta agonist) Patients who demonstrate an increase in FEV1 after inhaling a short acting beta agonist Exclusion Criteria: Asthma exacerbations in previous 6 months COPD or other pulmonary disease Excessive use of short acting beta agonists 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: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment A<br> | Drug: QAB149 75 mg Concept 1<br>* QAB149 delivered via the concept 1 device.<br>Other: Placebo EPIC Test Fixture<br>* Placebo administered via the EPIC Test Fixture.<br>|
| Experimental: Treatment B<br> | Drug: QAB149 75 mg Epic Test Fixture<br>* QAB149 delivered via the EPIC test fixture<br>Other: Placebo Concept 1<br>* Placebo administered via the Concept 1 device.<br>|
| Placebo Comparator: Treatment C<br> | Other: Placebo Concept 1<br>* Placebo administered via the Concept 1 device.<br>Other: Placebo EPIC Test Fixture<br>* Placebo administered via the EPIC Test Fixture.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Trough Forced Expiratory Volume in 1 Second (FEV1) Following 3 Days of Treatment | 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 was defined as the mean of two measurements at 23h 10min and 23h 45min post the Day 3 dose. | Day 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak Forced Expiratory Volume in 1 Second (FEV1) on Days 1 and 3 | Spirometry was conducted according to internationally accepted standards. Peak FEV1 is the maximum FEV1 recorded in the period between 5 minutes and 4 hours post dose on Days 1 and 3. | Days 1 and 3 | 
| Time to Peak Forced Expiratory Volume in 1 Second (FEV1) on Days 1 and 3 | Spirometry was conducted according to internationally accepted standards. Peak FEV1 is the maximum FEV1 recorded in the period between 5 minutes and 4 hours post dose on Days 1 and 3. | Days 1 and 3 | 
| Forced Vital Capacity (FVC) at Each Time-point on Day 1, 2, 3 and 4 | Spirometry was conducted according to internationally accepted standards. FVC was calculated at each time point up to 4 hours post-dose and at 23 hours 10 min and 23 hours 45 min on Days 1/2 and 3/4. | Days 1, 2, 3 and 4 | 
| Forced Expiratory Volume in 1 Second (FEV1) Standardized (With Respect to Length of Time) Area Under the Curve (AUC) From pre-dose to 4 hours post dose on Days 1 and 3 | FEV1 was measured with spirometry conducted according to internationally accepted standards. Measurements were made at 5, 15, and 30 minutes; and 1, 2, 3 and 4 hours post-dose. The standardized AUC FEV1 was calculated as the sum of trapezoids divided by the length of time. | Days 1 and 3 | 
| Peak Expiratory Flow Rate measured daily each morning and evening. | Peak Expiratory Flow (PEF) was measured every morning and evening from screening until study completion using a peak flow meter, and was recorded in the patient diary. | Morning and evening from screening to study completion (up to 86 days) | 
| Forced Expiratory Volume in 1 Second (FEV1) | Spirometry was conducted according to internationally accepted standards. Forced expiratory volume in 1 second (FEV1) is the amount of air that can be exhaled in one second. FEV1 was measured at each time point up to 4 hours on Days 1 and 3 and at 23hours 10 mins and 23 hours 45 mins on Days 2 and 4. | Days 1, 2, 3 and 4 | 
| Ratio of Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) (FEV1/FVC | Spirometry was conducted according to internationally accepted standards. FEV1/FVC represents the proportion of the total amount of air that is exhaled from the lungs during the first second of forced exhalation. FEV1/FVC was measured at each timepoint up to 4 hours on Days 1 and 3 and 23hours 10mins and 23hours 45 mins on Days 2 and 4. | Days 1, 2, 3, 4 | 
| Forced expiratory Flow 25-75% (FEF25-75%) | 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. FEF 25-75% was measured at each timepoint up to 4 hours on Days 1 and 3 and 23hours 10mins and 23hours 45 mins on Days 2 and 4 | Days 1, 2, 3, 4 | 
| Number of puffs of rescue medication used | Participants maintained a diary to record the daily number of puffs of rescue Short-acting B2 agonist (SABA) used to treat asthma symptoms. | Everyday from screening to study completion (up to 86 days) | 
| The number of participants with adverse events used as a measure of Safety and Tolerability | Safety and tolerability of indacaterol administered via the EPIC test fixture and the Concept1 was measured by collecting the following safety data: - number and percentage of adverse events reported by participants for the duration of the study - safety laboratory testing - measurement of vital signs (blood pressure and heart rate) - measurement of ECGs | Baseline to study completion (up to 59 days) | 
| AUC (0-24) - area under the serum concentration-time curve | The PK parameter AUC0-24 - area under the serum concentration-time curve - was determined from the serum concentration time profile of indacaterol on Days 1 and 3 from time zero to 24 hours post dose using a non-compartmental method | Day 1 and Day 3 (pre-dose, 5, 15, 30 mins, 1, 2, 4, 8, 12, 24hours post dose | 
| Cmax - observed maximum serum concentration following drug administration | The PK parameter Cmax - observed maximum serum concentration following drug administration - was determined from the serum concentration time profile of indacaterol on Days 1 and 3 using a non-compartmental method. | Day 1 and Day 3 (pre-dose, 5, 15, 30 mins, 1, 2, 4, 8, 12, 24hours post dose | 
| Tmax - time to reach maximum concentration after drug administration | The PK parameter Tmax - time to reach maximum concentration after drug administration - was determined from the serum concentration time profile of indacaterol on Days 1 and 3 using a non-compartmental method. | Day 1 and Day 3 (pre-dose, 5, 15, 30 mins, 1, 2, 4, 8, 12, 24hours post dose | 
| Racc - accumulation ratio of exposure (AUC0-24 and Cmax) on Day 3 relative to Day 1 | The PK parameter Racc - accumulation ratio of exposure (AUC0-24 and Cmax) on Day 3 relative to Day 1 - was determined from the serum concentration time profile of indacaterol on Days 1 and 3 using a non-compartmental method. | Day 1 and Day 3 (pre-dose, 5, 15, 30 mins, 1, 2, 4, 8, 12, 24hours post dose | 
| Trough Forced Expiratory Volume in 1 Second (FEV1) Following 1 Day of Treatment | 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 was defined as the mean of two measurements at 23h 10min and 23h 45min post the Day 1 dose. | Day 2 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Asthma, Indacaterol, QAB149