Efficacy, Safety, Tolerability, and Pharmacokinetics of Indacaterol Maleate Via Concept1 or Simoon Devices

Study Overview
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Brief Summary
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This study assessed the efficacy, safety, tolerability, and pharmacokinetics of two different formulations of indacaterol, one administered via the Concept1 device and one administered via the Simoon device. The study aimed to determine whether the novel formulation (Simoon) had a similar profile to that of the established formulation (Concept1).

Detailed Description
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This study was double-blind with regards to the Concept1, where placebo for the lactose-blended indacaterol was available. However, with regards to the Simoon, neither the subject nor the investigator was blinded due to lack of a placebo to the PulmoSphere formulation. Hence, the overall designation of the study was partially-blind.

Official Title
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A Randomized, Partially-blinded, Single-dose, 4-way Cross-over Study to Evaluate the Efficacy, Safety, Tolerability, and Pharmacokinetics of Orally Inhaled Indacaterol Maleate Administered Via the Concept1 Device or Via the Simoon Device

Conditions
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Asthma

Intervention / Treatment
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* Drug: Indacaterol 150 μg via the Concept1 dry-powder inhaler
* Drug: Indacaterol 60 μg via the Simoon dry-powder inhaler
* Drug: Indacaterol 120 μg via the Simoon dry-powder inhaler
* Drug: Placebo to indacaterol via the Concept1 dry-powder inhaler


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Patients with persistent asthma with a forced expiratory volume in 1 second (FEV1) ≥ 50% Patients using inhaled corticosteroid (with or without long-acting beta agonist) Exclusion criteria: Asthma exacerbations in previous 6 months Chronic obstructive pulmonary disease (COPD) or other pulmonary disease Excessive use of short-acting beta agonists Other protocol-defined inclusion/exclusion criteria applied to the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Indacaterol 150μg-placebo-Indacaterol 60μg-Indacaterol 120μg<br>In treatment period 1, patients received indacaterol 150 μg via the Concept1 dry-powder inhaler (DPI); in treatment period 2, patients received placebo to indacaterol via the Concept1 DPI; in treatment period 3, patients received indacaterol 60 μg via the Simoon DPI; and in treatment period 4, patients received indacaterol 120 μg via the Simoon DPI. Patients received each treatment only once. There was a washout period of 14-17 days between treatments for patients undergoing pharmacokinetic (PK) assessments; for patients not undergoing PK assessments, the washout period was 7-10 days. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol was available for rescue use throughout the study. | Drug: Indacaterol 150 μg via the Concept1 dry-powder inhaler<br>* Indacaterol maleate 150 μg was provided in powder filled capsules with the Concept1 dry-powder inhaler.<br>Drug: Indacaterol 60 μg via the Simoon dry-powder inhaler<br>* Indacaterol 60 μg was provided in powder filled capsules with the Simoon dry-powder inhaler.<br>Drug: Indacaterol 120 μg via the Simoon dry-powder inhaler<br>* Indacaterol 120 μg was provided in powder filled capsules with the Simoon dry-powder inhaler.<br>Drug: Placebo to indacaterol via the Concept1 dry-powder inhaler<br>* Placebo to indacaterol was provided in powder filled capsules with the Concept1 dry-powder inhaler.<br>|
| Experimental: Indacaterol 60μg-Indacaterol 150μg-Indacaterol 120μg-placebo<br>In treatment period 1, patients received indacaterol 60 μg via the Simoon dry-powder inhaler (DPI); in treatment period 2, patients received indacaterol 150 μg via the Concept1 DPI; in treatment period 3, patients received indacaterol 120 μg via the Simoon DPI; and in treatment period 4, patients received placebo to indacaterol via the Concept1 DPI. Patients received each treatment only once. There was a washout period of 14-17 days between treatments for patients undergoing pharmacokinetic (PK) assessments; for patients not undergoing PK assessments, the washout period was 7-10 days. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol was available for rescue use throughout the study. | Drug: Indacaterol 150 μg via the Concept1 dry-powder inhaler<br>* Indacaterol maleate 150 μg was provided in powder filled capsules with the Concept1 dry-powder inhaler.<br>Drug: Indacaterol 60 μg via the Simoon dry-powder inhaler<br>* Indacaterol 60 μg was provided in powder filled capsules with the Simoon dry-powder inhaler.<br>Drug: Indacaterol 120 μg via the Simoon dry-powder inhaler<br>* Indacaterol 120 μg was provided in powder filled capsules with the Simoon dry-powder inhaler.<br>Drug: Placebo to indacaterol via the Concept1 dry-powder inhaler<br>* Placebo to indacaterol was provided in powder filled capsules with the Concept1 dry-powder inhaler.<br>|
| Experimental: Indacaterol 120μg-Indacaterol 60μg-placebo-Indacaterol 150μg<br>In treatment period 1, patients received indacaterol 120 μg via the Simoon dry-powder inhaler (DPI); in treatment period 2, patients received indacaterol 60 μg via the Simoon DPI; in treatment period 3, patients received placebo to indacaterol via the Concept1 DPI; and in treatment period 4, patients received indacaterol 150 μg via the Concept1 DPI. Patients received each treatment only once. There was a washout period of 14-17 days between treatments for patients undergoing pharmacokinetic (PK) assessments; for patients not undergoing PK assessments, the washout period was 7-10 days. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol was available for rescue use throughout the study. | Drug: Indacaterol 150 μg via the Concept1 dry-powder inhaler<br>* Indacaterol maleate 150 μg was provided in powder filled capsules with the Concept1 dry-powder inhaler.<br>Drug: Indacaterol 60 μg via the Simoon dry-powder inhaler<br>* Indacaterol 60 μg was provided in powder filled capsules with the Simoon dry-powder inhaler.<br>Drug: Indacaterol 120 μg via the Simoon dry-powder inhaler<br>* Indacaterol 120 μg was provided in powder filled capsules with the Simoon dry-powder inhaler.<br>Drug: Placebo to indacaterol via the Concept1 dry-powder inhaler<br>* Placebo to indacaterol was provided in powder filled capsules with the Concept1 dry-powder inhaler.<br>|
| Experimental: Placebo-Indacaterol 120μg- Indacaterol 150μg- Indacaterol 60μg<br>In treatment period 1, patients received placebo to indacaterol via the Concept1 dry-powder inhaler (DPI); in treatment period 2, patients received indacaterol 120 μg via the Simoon DPI; in treatment period 3, patients received indacaterol 150 μg via the Concept1 DPI; and in treatment period 4, patients received indacaterol 60 μg via the Simoon DPI. Patients received each treatment only once. There was a washout period of 14-17 days between treatments for patients undergoing pharmacokinetic (PK) assessments; for patients not undergoing PK assessments, the washout period was 7-10 days. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol was available for rescue use throughout the study. | Drug: Indacaterol 150 μg via the Concept1 dry-powder inhaler<br>* Indacaterol maleate 150 μg was provided in powder filled capsules with the Concept1 dry-powder inhaler.<br>Drug: Indacaterol 60 μg via the Simoon dry-powder inhaler<br>* Indacaterol 60 μg was provided in powder filled capsules with the Simoon dry-powder inhaler.<br>Drug: Indacaterol 120 μg via the Simoon dry-powder inhaler<br>* Indacaterol 120 μg was provided in powder filled capsules with the Simoon dry-powder inhaler.<br>Drug: Placebo to indacaterol via the Concept1 dry-powder inhaler<br>* Placebo to indacaterol was provided in powder filled capsules with the Concept1 dry-powder inhaler.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) 24 Hours Post-dose for Each Treatment | FEV1 was measured with spirometry conducted according to internationally accepted standards. Trough FEV1 was defined as the average of measurements made 23 hours 10 minutes and 23 hours 45 minutes post-dose for each treatment. | Baseline and Day 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Peak Forced Expiratory Volume in 1 Second (FEV1) for Each Treatment | FEV1 was measured with spirometry conducted according to internationally accepted standards. Measurements were made at 5, 15, and 30 minutes; and 1, 2, 4, 6, 8, and 12 hours post-dose in Day 1. | Baseline and Day 1 | 
| Time to Peak Forced Expiratory Volume in 1 Second (FEV1) for Each Treatment | FEV1 was measured with spirometry conducted according to internationally accepted standards at 5, 15, and 30 minutes; 1 hour, 1 hour 30 minutes; and 1, 2, 4, 6, 8, and 12 hours post-dose in Day 1. | From 5 minutes to 12 hours post-dose | 
| Forced Expiratory Volume in 1 Second (FEV1) Standardized (With Respect to Length of Time) Area Under the Curve (AUC) From 5 Minutes to 4 Hours Post-dose for Each Treatment | FEV1 was measured with spirometry conducted according to internationally accepted standards. Measurements were made at 5, 15, and 30 minutes; and 1, 2, and 4 hours post-dose. The standardized AUC FEV1 was calculated as the sum of trapezoids divided by the length of time. | From 5 minutes to 4 hours post-dose for each treatment | 
| Indacaterol Exposure (AUC[0-24 Hours]) for Each Treatment | All patients fasted for at least 10 hours prior to administration of study medication and continued to fast for at least 4 hours thereafter. Venous blood samples for pharmacokinetic evaluation were collected at 5, 10, 15, and 30 minutes; and 1, 2, 4, 8, and 24 hours post-dose in each treatment period and were analyzed using a LC-MS/MS assay. Area under the concentration-time curve up to 24 hours (AUC[0-24 hours]) was calculated from concentration-time data using non-compartmental analysis. | 0 to 24 hours post-dose | 
| Indacaterol Exposure (Cmax) for Each Treatment | All patients fasted for at least 10 hours prior to administration of study medication and continued to fast for at least 4 hours thereafter. Venous blood samples for pharmacokinetic evaluation were collected at 5, 10, 15, and 30 minutes; and 1, 2, 4, 8, and 24 hours post-dose in each treatment period and were analyzed using a LC-MS/MS assay. Maximum (peak) plasma drug concentration after drug administration (Cmax) was calculated from concentration-time data using non-compartmental analysis. | 0 to 24 hours post-dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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asthma, QAB149, indacaterol, pulmonary function