A Study to Evaluate the Effects of Indacaterol Maleate as a New Formulation in the Concept 1 Device

Study Overview
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Brief Summary
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This study will assess the pharmacodynamics, safety, tolerability and pharmacokinetics of two different formulations of indacaterol maleate, both administered via the Concept1 device. The study aims to determine whether the novel formulation has a similar clinical profile as the established formulation.

Official Title
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A Multi-centre, Randomized, Double-blind, Double-dummy, Multiple-dose, Crossover Study to Evaluate the Pharmacodynamics, Pharmacokinetics, Safety and Tolerability of Orally Inhaled Indacaterol Administered as Either PulmoSphere or Lactose-blend Powder Via the Concept1 Device in Adult Patients With Persistent Asthma

Conditions
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Asthma

Intervention / Treatment
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* Drug: 75 µg indacaterol maleate (LB)
* Drug: 75 µg indacaterol maleate (PoS)
* Drug: 37.5 µg indacaterol maleate (PoS)
* Drug: placebo to indacaterol (LB)
* Drug: placebo to indacaterol (PoS)


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

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 75 µg Indacaterol (LB) + Placebo (PoS)<br>75 µg indacaterol maleate lactose blend (LB) + placebo to indacterol PulmoSphereTM (PoS) delivered via the Concept1 device once daily in the morning for 7 days. | Drug: 75 µg indacaterol maleate (LB)<br>* 75 µg indacaterol maleate lactose blend (LB) delivered via the Concept1 device once daily in the morning for 7 days.<br>Drug: placebo to indacaterol (PoS)<br>* Placebo to indacaterol PulmoSphereTM (PoS) delivered via the Concept1 device once daily in the morning for 7 days.<br>|
| Experimental: 75 µg Indacaterol (PoS) + Placebo (LB)<br>75 µg indacaterol maleate PulmoSphereTM (PoS) + placebo to indacterol lactose blend (LB) delivered via the Concept1 device once daily in the morning for 7 days. | Drug: 75 µg indacaterol maleate (PoS)<br>* 75 µg indacaterol maleate PulmoSphereTM (PoS) delivered via the Concept1 device once daily in the morning for 7 days.<br>Drug: placebo to indacaterol (LB)<br>* Placebo to indacaterol lactose blend (LB) delivered via the Concept1 device once daily in the morning for 7 days.<br>|
| Experimental: 37.5 µg Indacaterol (PoS) + Placebo (LB)<br>37.5 µg indacaterol maleate PulmoSphereTM (PoS) + placebo to indacaterol lactose blend (LB) delivered via the Concept1 device once daily in the morning for 7 days. | Drug: 37.5 µg indacaterol maleate (PoS)<br>* 37.5 µg indacaterol maleate PulmoSphereTM (PoS) delivered via the Concept1 device once daily in the morning for 7 days.<br>Drug: placebo to indacaterol (LB)<br>* Placebo to indacaterol lactose blend (LB) delivered via the Concept1 device once daily in the morning for 7 days.<br>|
| Experimental: Placebo (LB) and Placebo (PoS)<br>Placebo to indacaterol PulmoSphereTM (PoS) + placebo to indacaterol lactose blend (LB) delivered via the Concept1 device once daily in the morning for 7 days. | Drug: placebo to indacaterol (LB)<br>* Placebo to indacaterol lactose blend (LB) delivered via the Concept1 device once daily in the morning for 7 days.<br>Drug: placebo to indacaterol (PoS)<br>* Placebo to indacaterol PulmoSphereTM (PoS) delivered via the Concept1 device once daily in the morning for 7 days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Trough Forced Expiratory Volume in One Second (FEV1) After 7 Days of Treatment | Spirometry was performed according to internationally accepted standards at Day 8. Trough FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation. Trough FEV1 was defined as the average of the FEV1 measurements at 23 hours 10 minutes and 23 hours 45 minutes post dose.at Day 8. Analysis of Covariance with treatment, period, sequence and subject nested within sequence as fixed effects and period FEV1 baseline as a covariate. | Day 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Trough Forced Expiratory Volume in One Second (FEV1) After 1 Day of Treatment | Spirometry was performed according to internationally accepted standards at Day 2. Trough FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation. Trough FEV1 was defined as the average of the FEV1 measurements at 23 hours 10 minutes and 23 hours 45 minutes post dose at Day 2. Analysis of Covariance with treatment, period, sequence and subject nested within sequence as fixed effects and period FEV1 baseline as a covariate. | Day 2 | 
| Peak FEV1 at Day 1 and Day 7 | Spirometry was performed according to internationally accepted standards at 0, 15 and 30 minutes; 1,2,3,4,8,12 hours on Day 1 and 23.16 and 23.75 hours on Day 2 after 1 day of treatment and on Day 7 and Day 8 following 7 days of treatment. Peak FEV1 was the maximum FEV1 post treatment. Analysis of Covariance with treatment, period, sequence and subject nested within sequence as fixed effects and period FEV1 baseline included as a covariate. | Day 1, Day 7 | 
| Time to Peak FEV1 at Day 1 and Day 7 | Spirometry was performed according to internationally accepted standards. Time to the peak (maximum) FEV1 is recorded. Analysis of Covariance with treatment, period, sequence and subject nested within sequence as fixed effects and period FEV1 baseline as a covariate. | Day 1, Day 7 | 
| FEV1 at Each Time-Point on Day 1 and Day 2 | Spirometry was conducted according to internationally accepted standards post-dose at 0, 15 and 30 minutes; 1, 2, 3, 4, 8, 12 hours on Day 1 and 23.16 and 23.75 hours on Day 2. FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation. | Day 1, Day 2 | 
| FEV1 at Each Time-Point on Day 7 and Day 8 | Spirometry was conducted according to internationally accepted standards at 0, 15 and 30 minutes; 1,2,3,4,8,12 hours on Day 7 and 23.16 and 23.75 hours on Day 8. FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation. | Day 7, Day 8 | 
| Forced Vital Capacity (FVC) at Each Time-Point on Day 1 and Day 2 | Spirometry was conducted according to internationally accepted standards post-dose at 0, 15 and 30 minutes; 1, 2, 3, 4, 8 and 12 hours on Day 1 and 23.16 and 23.75 hours on Day 2. FVC is the amount of air that can be forcibly exhaled from the lungs after taking the deepest breath possible. | Day 1, Day 2 | 
| Forced Vital Capacity (FVC) at Each Time-Point on Day 7 and Day 8 | Spirometry was conducted according to internationally accepted standards post-dose at 0, 15 and 30 minutes; 1, 2, 3, 4, 8 and 12 hours on Day 7 and 23.16 and 23.75 hours on Day 8. FVC is the amount of air that can be forcibly exhaled from the lungs after taking the deepest breath possible. | Day 7, Day 8 | 
| FEV1/FVC at Each Post-Dose Time Point on Day 1 and Day 2 | Spirometry was conducted according to internationally accepted standards post-dose at 0, 15 and 30 minutes; 1, 2, 3, 4, 8 and 12 hours on Day 1 and 23.16 and 23.75 hours on Day 2. FEV1/FVC ratio is the percentage of the total FVC that is expelled from the lungs during the first second of forced exhalation. | Day1, Day 2 | 
| FEV1/FVC at Each Post-dose Time Point on Day 7 and Day 8 | Spirometry was conducted according to internationally accepted standards post-dose at 0, 15 and 30 minutes; 1, 2, 3, 4, 8 and 12 hours on Day 1 and 23.16 and 23.75 hours on Day 2 after treatment. FEV1/FVC ratio is the percentage of the total FVC that is expelled from the lungs during the first second of forced exhalation. | Day 7, Day 8 | 
| Forced Expiratory Flow 25- 75% (FEF25-75) on Day 1 and Day 2 | Spirometry was conducted according to internationally accepted standards post-dose at 0, 15 and 30 minutes; 1, 2, 3, 4, 8 and 12 hours on Day 1 and 23.16 and 23.75 hours on Day 2. 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. | Day 1, Day 2 | 
| Forced Expiratory Flow 25- 75% (FEF25-75) on Day 7 and Day 8 | Spirometry was conducted according to internationally accepted standards post-dose at 0, 15 and 30 minutes; 1, 2, 3, 4, 8 and 12 hours on Day 7 and 23.16 and 23.75 hours on Day 8. 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. | Day 7, Day 8 | 
| Standardized FEV1 AUC Between Baseline (Pre-dose) and 4 Hour Post-dose (AUC0-4h) | Spirometry was conducted according to internationally accepted standards at predose, 5, 15 and 30 minutes, 1, 2 and 4 hours post-dose on Day 1 and Day 7. The standardized (with respect to the length of time) area under the curve (AUC) for FEV1 was calculated using trapezoidal rule between 5 min and 4 h post. Analysis of Covariance with treatment, period, sequence and subject nested within sequence as fixed effects and period FEV1 baseline as a covariate. | Day 1, Day 7 | 
| Standardized FEV1 AUC Between Baseline (Pre-dose) and 12 Hour Post-dose (AUC0-12h) | Spirometry was conducted according to internationally accepted standards at predose, 5 , 15 and 30 min, 1, 2, 4, 8 and 12 hours post-dose on Day 1 and Day 7. The standardized (with respect to the length of time) area under the curve (AUC) for FEV1 was calculated using trapezoidal rule between 5 min and 12 h post. Analysis of covariance with treatment, period, sequence and subject nested within sequence as fixed effects and FEV1 period baseline as a covariate. | Day 1, Day 7 | 
| Peak Expiratory Flow Rate in the Morning in the Evening | PEFR was measured on all days from Screening Visit 2 to end of study visit: twice daily pre-dose (prior to Inhaled Corticosteroids) and approximately 12 hours post-dose (during the treatment period). Each subject was provided with a PEFR meter and recorded the PEFR readings in a daily diary. repeated measures. Analysis of covariance with treatment, period, sequence, day and treatment-day interaction as fixed effect and subject as a random effect and baseline PEFR as a covariate in the model. | Up to 101 days | 
| Number of Puffs of Rescue Medicine | Salbutamol (100 µg/puff) was used as rescued medicine. The total number of puffs per day was calculated and divided by the number of days with data to determine the mean daily number of puffs of rescue medication for each patient and was recorded in the patient diary from Baseline until Day 8 of Treatment Period 4. Analysis of covariance with treatment, period, sequence, and subject nested within sequence as fixed effect. | Up to 101 days | 
| Number of Participants With Adverse Events as a Measure of Safety | Adverse event are defined as any unfavorable and unintended diagnosis, symptoms, sign (including an abnormal lab finding), syndrome or disease which either occurs during the study, having been absent at baseline, or if present at baseline appear to worsen. Serious adverse events are any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization , cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgments of the investigators represent significant hazards. Additional information about adverse events can be found in the Adverse Event section | Up to 101 days | 
| Time to Reach Maximum Concentration (Tmax) After Drug Administration |  | Day1, Day 7 | 
| Observed Maximum Concentration (Cmax) After Drug Administration |  | Day 1, Day 7 | 
| Area Under the Curve Pre-dose to 24 Hour Post Dose (AUC0-24h) |  | Day 1, Day 7 | 

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